Regulatable fusogenic oncolytic herpes simplex virus type 1 virus and methods of use

ABSTRACT

Malignant tumors that are resistant to conventional therapies represent significant therapeutic challenges. An embodiment of the present invention provides a regulatable fusogenic oncolytic herpes simplex virus-1 that is more effective at selective killing target cells, such as tumor cells. In various embodiments presented herein, the oncolytic virus described herein is suitable for treatment of solid tumors, as well as other cancers.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims benefit under 35 U.S.C. § 119(e) of U.S.Provisional Application No. 62/769,280 filed Nov. 19, 2018, the contentsof which is incorporated herein by reference in its entirety.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has beensubmitted electronically in ASCII format and is hereby incorporated byreference in its entirety. Said ASCII copy, created on Nov. 6, 2019, isnamed 043214-089130WOPT_SL.txt and is 210,810 bytes in size.

FIELD OF INVENTION

The present invention is directed compositions and methods of treatingcancer using regulatable fusogenic oncolytic herpes simplex virus 1(HSV-1) virus.

BACKGROUND

Oncolytic viral therapy entails harnessing the ability of a virus toreproduce in and lyse human cells and directing this viralreplication-dependent lysis preferentially toward cancerous cells.Advances in cancer biology, together with a detailed understanding ofthe roles of host factors and virus-encoded gene products in controllingvirus production in infected cells, have facilitated the use of someviruses as potential therapeutic agents against cancer (Aghi andMartuza, 2005; Parato et al., 2005). Herpes simplex virus (HSV)possesses several unique properties as an oncolytic agent (Aghi andMartuza, 2005). It can infect a broad range of cell types, leading tothe replication of new virus and cell death. HSV has a short replicationcycle (9 to 18 h) and encodes many non-essential genes that, whendeleted, greatly restrict the ability of the virus to replicate innon-dividing normal cells. Because of its large genome, multipletherapeutic genes can be packaged into the genome of oncolyticrecombinants.

The use of a replication-conditional strain of HSV-1 as an oncolyticagent was first reported for the treatment of malignant gliomas (Martuzaet al., 1991). Since then, various efforts have been made in an attemptto broaden their therapeutic efficacy and increase the replicationspecificity of the virus in tumor cells. Not surprisingly, however,deletion of genes that impair viral replication in normal cells alsoleads to a marked decrease in the oncolytic activity of the virus forthe targeted tumor cells (Advani et al., 1998; Chung et al., 1999).Currently, no oncolytic viruses that are able to kill only tumor cellswhile leaving normal cells intact are available. Consequently, thetherapeutic doses of existing oncolytic viruses are significantlyrestricted (Aghi and Martuza, 2005). The availability of an oncolyticvirus whose replication can be tightly controlled and adjustedpharmacologically would offer greatly increased safety and therapeuticefficacy. Such a regulatable oncolytic virus would minimize unwantedreplication in adjacent and distant tissues as well as undesirableprogeny virus overload in the target area after the tumor has beeneliminated. This regulatory feature would also allow the oncolyticactivity of the virus to be quickly shut down should adverse effects bedetected (Aghi and Martuza, 2005; Shen and Nemunaitis, 2005). Workdescribed herein presents a regulatable fusogenic variant of a oncolyticHSV that is significantly more effective at killing cancer cells thanits non-fusogenic parent.

SUMMARY OF THE INVENTION

The invention described herein is based, in part, on an isolatedfusogenic variant of a novel oncolytic HSV-1 recombinant, KTR27, whosereplication can be tightly controlled and regulated by tetracycline in adose-dependent manner (Yao et al., J Virol, 2010) (U.S. Pat. No.8,236,941). Work described herein demonstrates that this fusogenicvariant, KTR27-F, is significantly more superior to its non-fusogenicparent in lysing various tested human cancer cells. Like KTR27,replication of KTR27-F in primary human fibroblasts is markedly reducedcompared with various human tumor cells. The yield of KTR27-F in humanbreast cancer cells (MCF-7) is 21,800-fold higher than ingrowth-arrested normal human breast fibroblasts. Moreover, whileinfection of growth-arrested human breast fibroblasts with KTR27 inducedlittle or no cytotoxicity in the infected cells, over 99% of infectedMCF7 cells were non-viable compared with the mock-infected control.Collectively, KTR27-F represents proof-of-concept advancement in thedesign of safer and more effective oncolytic viruses.

Accordingly, one aspect described herein provides an oncolytic HerpesSimplex Virus (HSV) comprising recombinant DNA, wherein the recombinantDNA has both ICP0 and ICP34.5 gene deleted or does not expressfunctional ICP0 and ICP34.5

Another aspect described herein provides an oncolytic Herpes SimplexVirus (HSV) comprising recombinant DNA, wherein the recombinant DNAcomprises: a gene comprising a 5′ untranslated region and a HSV-1, orHSV-2, ICP27 gene that is operably linked to an ICP27 promotercomprising a TATA element; a tetracycline operator sequence positionedbetween 6 and 24 nucleotides 3′ to said TATA element, wherein the ICP27gene lies 3′ to said tetracycline operator sequence; a ribozyme sequencelocated in said 5′ untranslated region of said gene; a gene sequenceencoding tetracycline repressor operably linked to an immediate-earlypromoter, wherein the gene sequence is located at the ICP0 locus; and avariant gene that increases syncytium formation as compared to wildtype, wherein the HSV-1, or HSV-2, variant gene is selected from thegroup consisting of: a glycoprotein K (gK) variant; a glycoprotein B(gB) variant; a UL24 variant; and UL20 gene variant, wherein saidoncolytic HSV does not encode functional ICP0 and functional ICP34.5protein.

In one embodiment of any aspect, the variant gene is a gK variant genethat encodes an amino acid substitution selected from the groupconsisting of: an Ala to Val amino acid substitution corresponding toamino acid 40 of SEQ ID NO: 2; an Ala to “x” amino acid substitutioncorresponding to amino acid 40 of SEQ ID NO: 2, wherein “x” is any aminoacid; an Asp to Asn amino acid substitution corresponding to amino acid99 of SEQ ID NO: 2; a Leu to Pro amino acid substitution correspondingto amino acid 304 of SEQ ID NO: 2; and an Arg to Leu amino acidsubstitution corresponding to amino acid 310 of SEQ ID NO: 2. In oneembodiment, the oncolytic HSV further comprises a variant UL24 gene thatencodes a Ser to Asn amino acid substitution corresponding to amino acid113 of SEQ ID NO: 3. In one embodiment of any aspect, the variant geneis a UL24 gene that encodes a Ser to Asn amino acid substitutioncorresponding to amino acid 113 of SEQ ID NO: 3. In one embodiment, theamino acids described herein can be substituted for any known aminoacid.

In one embodiment of any aspect, the tetracycline operator sequencecomprises two Op2 repressor binding sites.

In one embodiment of any aspect, the ICP27 promoter is an HSV-1 or HSV-2ICP27 promoter.

In one embodiment of any aspect, the immediate-early promoter is anHSV-1 or HSV-2 immediate-early promoter or the HCMV immediate-earlypromoter.

In one embodiment of any aspect, the HSV immediate-early promoter isselected from the group consisting of: ICP0 promoter, ICP4 promoter,ICP27 promoter, and ICP22 promoter.

In one embodiment of any aspect, the recombinant DNA is part of theHSV-1 genome. In one embodiment of any aspect, the recombinant DNA ispart of the HSV-2 genome.

In one embodiment of any aspect, the oncolytic HSV described hereinfurther comprises a pharmaceutically acceptable carrier

In one embodiment of any aspect, the oncolytic HSV described hereinfurther encodes at least one polypeptide that can increase the efficacyof the oncolytic HSV to induce an anti-tumor-specific immunity. In oneembodiment, the at least one polypeptide encodes a product selected fromthe group consisting of: interleukin 2 (IL2), interleukin 12 (IL12),interleukin 15 (IL15), an anti-PD-1 antibody or antibody reagent, ananti-PD-L1 antibody or antibody reagent, an anti-OX40 antibody orantibody reagent, CTLA-4 antibody or antibody reagent, TIM-3 antibody orantibody reagent, and TIGIT antibody or antibody reagent.

Another aspect described herein provides a composition comprising any ofthe oncolytic HSV described herein. In one embodiment, the compositionfurther comprises a pharmaceutically acceptable carrier.

Another aspect described herein provides a method for treating cancercomprising administering any of the oncolytic HSV described herein or acomposition thereof to a subject having cancer.

In one embodiment of any aspect, the cancer is a solid tumor.

In one embodiment of any aspect, the tumor is benign or malignant.

In one embodiment of any aspect, the subject is diagnosed or has beendiagnosed as having a carcinoma, a melanoma, a sarcoma, a germ celltumor, or a blastoma. In one embodiment of any aspect, the subject isdiagnosed or has been diagnosed as having non-small-cell lung cancer,breast cancer, brain cancer, colon cancer, prostate cancer, livercancer, lung cancer, ovarian cancer, skin cancer, and pancreatic cancer.

In one embodiment of any aspect, the cancer is metastatic.

In one embodiment of aspect, the oncolytic HSV is administered directlyto the tumor.

In one embodiment of any aspect, the method further comprisesadministering an agent that regulates the tet operator. In oneembodiment, the agent is doxycycline or tetracycline. In one embodiment,the agent is administered locally or systemically.

Definitions

All references cited herein are incorporated by reference in theirentirety as though fully set forth.

Unless otherwise defined herein, scientific and technical terms used inconnection with the present application shall have the meanings that arecommonly understood by those of ordinary skill in the art to which thisdisclosure belongs. It should be understood that this invention is notlimited to the particular methodology, protocols, and reagents, etc.,described herein and as such can vary. Definitions of common terms canbe found in Singleton et al., Dictionary of Microbiology and MolecularBiology 3^(rd) ed., J. Wiley & Sons New York, N.Y. (2001); March,Advanced Organic Chemistry Reactions, Mechanisms and Structure 5^(th)ed., J. Wiley & Sons New York, N.Y. (2001); Michael Richard Green andJoseph Sambrook, Molecular Cloning: A Laboratory Manual, 4th ed., ColdSpring Harbor Laboratory Press, Cold Spring Harbor, N.Y., USA (2012);Davis et al., Basic Methods in Molecular Biology, Elsevier SciencePublishing, Inc., New York, USA (2012); Jon Lorsch (ed.) LaboratoryMethods in Enzymology: DNA, Elsevier, (2013); Frederick M. Ausubel(ed.), Current Protocols in Molecular Biology (CPMB), John Wiley andSons, (2014); John E. Coligan (ed.), Current Protocols in ProteinScience (CPPS), John Wiley and Sons, Inc., (2005); and Ethan M Shevach,Warren Strobe, (eds.) Current Protocols in Immunology (CPI) (John E.Coligan, ADA M Kruisbeek, David H Margulies, John Wiley and Sons, Inc.,(2003); each of which provide one skilled in the art with a generalguide to many of the terms used in the present application.

As used herein, a “subject” means a human or animal. Usually the animalis a vertebrate such as a primate, rodent, domestic animal or gameanimal. Primates include, for example, chimpanzees, cynomologousmonkeys, spider monkeys, and macaques, e.g., Rhesus. Rodents include,for example, mice, rats, woodchucks, ferrets, rabbits and hamsters.Domestic and game animals include, for example, cows, horses, pigs,deer, bison, buffalo, feline species, e.g., domestic cat, caninespecies, e.g., dog, fox, wolf, avian species, e.g., chicken, emu,ostrich, and fish, e.g., trout, catfish and salmon. In some embodiments,the subject is a mammal, e.g., a primate, e.g., a human. The terms,“individual,” “patient” and “subject” are used interchangeably herein.

Preferably, the subject is a mammal. The mammal can be a human,non-human primate, mouse, rat, dog, cat, horse, or cow, but is notlimited to these examples. Mammals other than humans can beadvantageously used as subjects that represent animal models of diseasee.g., cancer. A subject can be male or female.

A subject can be one who has been previously diagnosed with oridentified as suffering from or having a condition in need of treatment(e.g. cancer) or one or more complications related to such a condition,and optionally, have already undergone treatment for the condition orthe one or more complications related to the condition. Alternatively, asubject can also be one who has not been previously diagnosed as havingsuch condition or related complications. For example, a subject can beone who exhibits one or more risk factors for the condition or one ormore complications related to the condition or a subject who does notexhibit risk factors.

As used herein, the terms “treat,” “treatment,” “treating,” or“amelioration” refer to therapeutic treatments, wherein the object is toreverse, alleviate, ameliorate, inhibit, slow down or stop theprogression or severity of a condition associated with a disease ordisorder, e.g. cancer. The term “treating” includes reducing oralleviating at least one adverse effect or symptom of a condition,disease or disorder. Treatment is generally “effective” if one or moresymptoms or clinical markers are reduced. Alternatively, treatment is“effective” if the progression of a disease is reduced or halted. Thatis, “treatment” includes not just the improvement of symptoms ormarkers, but also a cessation of, or at least slowing of, progress orworsening of symptoms compared to what would be expected in the absenceof treatment. Beneficial or desired clinical results include, but arenot limited to, alleviation of one or more symptom(s), diminishment ofextent of disease, stabilized (i.e., not worsening) state of disease,delay or slowing of disease progression, amelioration or palliation ofthe disease state, remission (whether partial or total), and/ordecreased mortality, whether detectable or undetectable. The term“treatment” of a disease also includes providing relief from thesymptoms or side-effects of the disease (including palliativetreatment).

In the various embodiments described herein, it is further contemplatedthat variants (naturally occurring or otherwise), alleles, homologs,conservatively modified variants, and/or conservative substitutionvariants of any of the particular polypeptides described areencompassed. As to amino acid sequences, one of ordinary skill willrecognize that individual substitutions, deletions or additions to anucleic acid, peptide, polypeptide, or protein sequence which alters asingle amino acid or a small percentage of amino acids in the encodedsequence is a “conservatively modified variant” where the alterationresults in the substitution of an amino acid with a chemically similaramino acid and retains the desired activity of the polypeptide. Suchconservatively modified variants are in addition to and do not excludepolymorphic variants, interspecies homologs, and alleles consistent withthe disclosure.

A given amino acid can be replaced by a residue having similarphysiochemical characteristics, e.g., substituting one aliphatic residuefor another (such as Ile, Val, Leu, or Ala for one another), orsubstitution of one polar residue for another (such as between Lys andArg; Glu and Asp; or Gln and Asn). Other such conservativesubstitutions, e.g., substitutions of entire regions having similarhydrophobicity characteristics, are well known. Polypeptides comprisingconservative amino acid substitutions can be tested in any one of theassays described herein to confirm that a desired activity, e.g.ligan-mediated receptor activity and specificity of a native orreference polypeptide is retained.

Amino acids can be grouped according to similarities in the propertiesof their side chains (in A. L. Lehninger, in Biochemistry, second ed.,pp. 73-75, Worth Publishers, New York (1975)): (1) non-polar: Ala (A),Val (V), Leu (L), Ile (I), Pro (P), Phe (F), Trp (W), Met (M); (2)uncharged polar: Gly (G), Ser (S), Thr (T), Cys (C), Tyr (Y), Asn (N),Gln (Q); (3) acidic: Asp (D), Glu (E); (4) basic: Lys (K), Arg (R), His(H). Alternatively, naturally occurring residues can be divided intogroups based on common side-chain properties: (1) hydrophobic:Norleucine, Met, Ala, Val, Leu, Ile; (2) neutral hydrophilic: Cys, Ser,Thr, Asn, Gln; (3) acidic: Asp, Glu; (4) basic: His, Lys, Arg; (5)residues that influence chain orientation: Gly, Pro; (6) aromatic: Trp,Tyr, Phe. Non-conservative substitutions will entail exchanging a memberof one of these classes for another class. Particular conservativesubstitutions include, for example; Ala into Gly or into Ser; Arg intoLys; Asn into Gln or into His; Asp into Glu; Cys into Ser; Gln into Asn;Glu into Asp; Gly into Ala or into Pro; His into Asn or into Gln; Ileinto Leu or into Val; Leu into Ile or into Val; Lys into Arg, into Glnor into Glu; Met into Leu, into Tyr or into Ile; Phe into Met, into Leuor into Tyr; Ser into Thr; Thr into Ser; Trp into Tyr; Tyr into Trp;and/or Phe into Val, into Ile or into Leu.

In some embodiments, a polypeptide described herein (or a nucleic acidencoding such a polypeptide) can be a functional fragment of one of theamino acid sequences described herein. As used herein, a “functionalfragment” is a fragment or segment of a peptide which retains at least50% of the wildtype reference polypeptide's activity according to anassay known in the art or described below herein. A functional fragmentcan comprise conservative substitutions of the sequences disclosedherein.

In some embodiments, a polypeptide described herein can be a variant ofa polypeptide or molecule as described herein. In some embodiments, thevariant is a conservatively modified variant. Conservative substitutionvariants can be obtained by mutations of native nucleotide sequences,for example. A “variant,” as referred to herein, is a polypeptidesubstantially homologous to a native or reference polypeptide, but whichhas an amino acid sequence different from that of the native orreference polypeptide because of one or a plurality of deletions,insertions or substitutions. Variant polypeptide-encoding DNA sequencesencompass sequences that comprise one or more additions, deletions, orsubstitutions of nucleotides when compared to a native or reference DNAsequence, but that encode a variant protein or fragment thereof thatretains activity of the non-variant polypeptide. A wide variety ofPCR-based site-specific mutagenesis approaches are known in the art andcan be applied by the ordinarily skilled artisan.

A variant amino acid or DNA sequence can be at least 90%, at least 91%,at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, atleast 97%, at least 98%, at least 99%, or more, identical to a native orreference sequence. The degree of homology (percent identity) between anative and a mutant sequence can be determined, for example, bycomparing the two sequences using freely available computer programscommonly employed for this purpose on the world wide web (e.g. BLASTp orBLASTn with default settings).

Alterations of the native amino acid sequence can be accomplished by anyof a number of techniques known to one of skill in the art. Mutationscan be introduced, for example, at particular loci by synthesizingoligonucleotides containing a mutant sequence, flanked by restrictionsites permitting ligation to fragments of the native sequence. Followingligation, the resulting reconstructed sequence encodes an analog havingthe desired amino acid insertion, substitution, or deletion.Alternatively, oligonucleotide-directed site-specific mutagenesisprocedures can be employed to provide an altered nucleotide sequencehaving particular codons altered according to the substitution,deletion, or insertion required. Techniques for making such alterationsare well established and include, for example, those disclosed by Walderet al. (Gene 42:133, 1986); Bauer et al. (Gene 37:73, 1985); Craik(BioTechniques, January 1985, 12-19); Smith et al. (Genetic Engineering:Principles and Methods, Plenum Press, 1981); and U.S. Pat. Nos.4,518,584 and 4,737,462, which are herein incorporated by reference intheir entireties. Any cysteine residue not involved in maintaining theproper conformation of a polypeptide also can be substituted, generallywith serine, to improve the oxidative stability of the molecule andprevent aberrant crosslinking. Conversely, cysteine bond(s) can be addedto a polypeptide to improve its stability or facilitate oligomerization.

As used herein, the term “DNA” is defined as deoxyribonucleic acid. Theterm “polynucleotide” is used herein interchangeably with “nucleic acid”to indicate a polymer of nucleosides. Typically, a polynucleotide iscomposed of nucleosides that are naturally found in DNA or RNA (e.g.,adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine,deoxythymidine, deoxyguanosine, and deoxycytidine) joined byphosphodiester bonds. However, the term encompasses molecules comprisingnucleosides or nucleoside analogs containing chemically or biologicallymodified bases, modified backbones, etc., whether or not found innaturally occurring nucleic acids, and such molecules may be preferredfor certain applications. Where this application refers to apolynucleotide it is understood that both DNA, RNA, and in each caseboth single- and double-stranded forms (and complements of eachsingle-stranded molecule) are provided. “Polynucleotide sequence” asused herein can refer to the polynucleotide material itself and/or tothe sequence information (i.e. the succession of letters used asabbreviations for bases) that biochemically characterizes a specificnucleic acid. A polynucleotide sequence presented herein is presented ina 5′ to 3′ direction unless otherwise indicated.

The term “operably linked,” as used herein, refers to the arrangement ofvarious nucleic acid molecule elements relative to each other such thatthe elements are functionally connected and are able to interact witheach other. Such elements may include, without limitation, a promoter,an enhancer, a polyadenylation sequence, one or more introns and/orexons, and a coding sequence of a gene of interest to be expressed. Thenucleic acid sequence elements, when operably linked, can act togetherto modulate the activity of one another, and ultimately may affect thelevel of expression of the gene of interest, including any of thoseencoded by the sequences described above.

The term “vector,” as used herein, refers to a carrier nucleic acidmolecule into which a nucleic acid sequence can be inserted forintroduction into a cell where it can be replicated. A nucleic acidsequence can be “exogenous,” which means that it is foreign to the cellinto which the vector is being introduced or that the sequence ishomologous to a sequence in the cell but in a position within the hostcell nucleic acid in which the sequence is ordinarily not found. Vectorsinclude plasmids, cosmids, viruses (bacteriophage, animal viruses, andplant viruses), and artificial chromosomes (e.g., YACs). One of skill inthe art would be well equipped to construct a vector through standardrecombinant techniques (see, for example, Maniatis et al., 1988 andAusubel et al., 1994, both of which are incorporated herein byreference). Additionally, the techniques described herein anddemonstrated in the referenced figures are also instructive with regardto effective vector construction.

The term “oncolytic HSV-1 vector” refers to a genetically engineeredHSV-1 virus corresponding to at least a portion of the genome of HSV-1that is capable of infecting a target cell, replicating, and beingpackaged into HSV-1 virions. The genetically engineered virus comprisesdeletions and or mutations and or insertions of nucleic acid that renderthe virus oncolytic such that the engineered virus replicates in- andkills-tumor cells by oncolytic activity. The virus may be attenuated ornon-attenuated. The virus may or may not deliver a transgene—thatdiffers from the HSV viral genome. In one embodiment, the oncolyticHSV-1 vector does not express a transgene to produce a protein foreignto the virus.

The term “promoter,” as used herein, refers to a nucleic acid sequencethat regulates, either directly or indirectly, the transcription of acorresponding nucleic acid coding sequence to which it is operablylinked. The promoter may function alone to regulate transcription, or,in some cases, may act in concert with one or more other regulatorysequences such as an enhancer or silencer to regulate transcription ofthe gene of interest. The promoter comprises a DNA regulatory sequence,wherein the regulatory sequence is derived from a gene, which is capableof binding RNA polymerase and initiating transcription of a downstream(3′-direction) coding sequence. A promoter generally comprises asequence that functions to position the start site for RNA synthesis.The best-known example of this is the TATA box, but in some promoterslacking a TATA box, such as, for example, the promoter for the mammalianterminal deoxynucleotidyl transferase gene and the promoter for the SV40late genes, a discrete element overlying the start site itself helps tofix the place of initiation. Additional promoter elements regulate thefrequency of transcriptional initiation. Typically, these are located inthe region 30-110 bp upstream of the start site, although a number ofpromoters have been shown to contain functional elements downstream ofthe start site as well. To bring a coding sequence “under the controlof” a promoter, one can position the 5′ end of the transcriptioninitiation site of the transcriptional reading frame “downstream” of(i.e., 3′ of) the chosen promoter. The “upstream” promoter stimulatestranscription of the DNA and promotes expression of the encoded RNA.

The spacing between promoter elements frequently is flexible, so thatpromoter function is preserved when elements are inverted or movedrelative to one another. Depending on the promoter used, individualelements can function either cooperatively or independently to activatetranscription. The promoters described herein may or may not be used inconjunction with an “enhancer,” which refers to a cis-acting regulatorysequence involved in the transcriptional activation of a nucleic acidsequence, such as those for the genes, or portions or functionalequivalents thereof, listed herein.

A promoter may be one naturally associated with a nucleic acid sequence,as may be obtained by isolating the 5′ non-coding sequences locatedupstream of the coding segment and/or exon. Such a promoter can bereferred to as “endogenous.” Similarly, an enhancer may be one naturallyassociated with a nucleic acid sequence, located either downstream orupstream of that sequence. Alternatively, certain advantages may begained by positioning the coding nucleic acid segment under the controlof a recombinant or heterologous promoter, which refers to a promoterthat is not normally associated with a nucleic acid sequence in itsnatural environment. A recombinant or heterologous enhancer refers alsoto an enhancer not normally associated with a nucleic acid sequence inits natural environment. Such promoters or enhancers may includepromoters or enhancers of other genes, and promoters or enhancersisolated from any other virus, or prokaryotic or eukaryotic cell, andpromoters or enhancers not “naturally occurring,” i.e., containingdifferent elements of different transcriptional regulatory regions,and/or mutations that alter expression. For example, promoters that aremost commonly used in recombinant DNA construction include, the HCMVimmediate-early promoter, the beta-lactamase (penicillinase), lactoseand tryptophan (trp) promoter systems.

A “gene,” or a “sequence which encodes” a particular protein, is anucleic acid molecule which is transcribed (in the case of DNA) andtranslated (in the case of mRNA) into a polypeptide in vitro or in vivowhen placed under the control of one or more appropriate regulatorysequences. A gene of interest can include, but is no way limited to,cDNA from eukaryotic mRNA, genomic DNA sequences from eukaryotic DNA,and even synthetic DNA sequences. A transcription termination sequencewill usually be located 3′ to the gene sequence. Typically, apolyadenylation signal is provided to terminate transcription of genesinserted into a recombinant virus.

The term “polypeptide” as used herein refers to a polymer of aminoacids. The terms “protein” and “polypeptide” are used interchangeablyherein. A peptide is a relatively short polypeptide, typically betweenabout 2 and 60 amino acids in length. Polypeptides used herein typicallycontain amino acids such as the 20 L-amino acids that are most commonlyfound in proteins. However, other amino acids and/or amino acid analogsknown in the art can be used. One or more of the amino acids in apolypeptide may be modified, for example, by the addition of a chemicalentity such as a carbohydrate group, a phosphate group, a fatty acidgroup, a linker for conjugation, functionalization, etc. A polypeptidethat has a nonpolypeptide moiety covalently or noncovalently associatedtherewith is still considered a “polypeptide.” Exemplary modificationsinclude glycosylation and palmitoylation. Polypeptides can be purifiedfrom natural sources, produced using recombinant DNA technology orsynthesized through chemical means such as conventional solid phasepeptide synthesis, etc. The term “polypeptide sequence” or “amino acidsequence” as used herein can refer to the polypeptide material itselfand/or to the sequence information (i.e., the succession of letters orthree letter codes used as abbreviations for amino acid names) thatbiochemically characterizes a polypeptide. A polypeptide sequencepresented herein is presented in an N-terminal to C-terminal directionunless otherwise indicated.

The term “transgene” refers to a particular nucleic acid sequenceencoding a polypeptide or a portion of a polypeptide to be expressed ina cell into which the nucleic acid sequence is inserted. The term“transgene” is meant to include (1) a nucleic acid sequence that is notnaturally found in the cell (i.e., a heterologous nucleic acidsequence); (2) a nucleic acid sequence that is a mutant form of anucleic acid sequence naturally found in the cell into which it has beeninserted; (3) a nucleic acid sequence that serves to add additionalcopies of the same (i.e., homologous) or a similar nucleic acid sequencenaturally occurring in the cell into which it has been inserted; or (4)a silent naturally occurring or homologous nucleic acid sequence whoseexpression is induced in the cell into which it has been inserted. A“mutant form” or “modified nucleic acid” or “modified nucleotide”sequence means a sequence that contains one or more nucleotides that aredifferent from the wild-type or naturally occurring sequence, i.e., themutant nucleic acid sequence contains one or more nucleotidesubstitutions, deletions, and/or insertions. In some cases, the gene ofinterest may also include a sequence encoding a leader peptide or signalsequence such that the transgene product may be secreted from the cell.

As used herein, the term “antibody reagent” refers to a polypeptide thatincludes at least one immunoglobulin variable domain or immunoglobulinvariable domain sequence and which specifically binds a given antigen.An antibody reagent can comprise an antibody or a polypeptide comprisingan antigen-binding domain of an antibody. In some embodiments of any ofthe aspects, an antibody reagent can comprise a monoclonal antibody or apolypeptide comprising an antigen-binding domain of a monoclonalantibody. For example, an antibody can include a heavy (H) chainvariable region (abbreviated herein as VH), and a light (L) chainvariable region (abbreviated herein as VL). In another example, anantibody includes two heavy (H) chain variable regions and two light (L)chain variable regions. The term “antibody reagent” encompassesantigen-binding fragments of antibodies (e.g., single chain antibodies,Fab and sFab fragments, F(ab′)2, Fd fragments, Fv fragments, scFv, CDRs,and domain antibody (dAb) fragments (see, e.g. de Wildt et al., Eur J.Immunol. 1996; 26(3):629-39; which is incorporated by reference hereinin its entirety)) as well as complete antibodies. An antibody can havethe structural features of IgA, IgG, IgE, IgD, or IgM (as well assubtypes and combinations thereof). Antibodies can be from any source,including mouse, rabbit, pig, rat, and primate (human and non-humanprimate) and primatized antibodies. Antibodies also include midibodies,nanobodies, humanized antibodies, chimeric antibodies, and the like.

The term “oncolytic activity,” as used herein, refers to cytotoxiceffects in vitro and/or in vivo exerted on tumor cells without anyappreciable or significant deleterious effects to normal cells under thesame conditions. The cytotoxic effects under in vitro conditions aredetected by various means as known in prior art, for example, bystaining with a selective stain for dead cells, by inhibition of DNAsynthesis, or by apoptosis. Detection of the cytotoxic effects under invivo conditions is performed by methods known in the art.

A “biologically active” portion of a molecule, as used herein, refers toa portion of a larger molecule that can perform a similar function asthe larger molecule. Merely by way of non-limiting example, abiologically active portion of a promoter is any portion of a promoterthat retains the ability to influence gene expression, even if onlyslightly. Similarly, a biologically active portion of a protein is anyportion of a protein which retains the ability to perform one or morebiological functions of the full-length protein (e.g. binding withanother molecule, phosphorylation, etc.), even if only slightly.

As used herein, the term “administering,” refers to the placement of atherapeutic or pharmaceutical composition as disclosed herein into asubject by a method or route which results in at least partial deliveryof the agent at a desired site. Pharmaceutical compositions comprisingagents as disclosed herein can be administered by any appropriate routewhich results in an effective treatment in the subject.

The term “statistically significant” or “significantly” refers tostatistical significance and generally means a two standard deviation(2SD) or greater difference.

Other than in the operating examples, or where otherwise indicated, allnumbers expressing quantities of ingredients or reaction conditions usedherein should be understood as modified in all instances by the term“about.” The term “about” when used in connection with percentages canmean ±1%.

As used herein, the term “comprising” means that other elements can alsobe present in addition to the defined elements presented. The use of“comprising” indicates inclusion rather than limitation. The term“consisting of” refers to compositions, methods, and respectivecomponents thereof as described herein, which are exclusive of anyelement not recited in that description of the embodiment. As usedherein the term “consisting essentially of” refers to those elementsrequired for a given embodiment. The term permits the presence ofadditional elements that do not materially affect the basic and novel orfunctional characteristic(s) of that embodiment of the technology.

The singular terms “a,” “an,” and “the” include plural referents unlesscontext clearly indicates otherwise. Similarly, the word “or” isintended to include “and” unless the context clearly indicatesotherwise. Although methods and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of thisdisclosure, suitable methods and materials are described below. Theabbreviation, “e.g.” is derived from the Latin exempli gratia, and isused herein to indicate a non-limiting example. Thus, the abbreviation“e.g.” is synonymous with the term “for example.”

In some embodiments, the numbers expressing quantities of ingredients,properties such as molecular weight, reaction conditions, and so forth,used to describe and claim certain embodiments of the application are tobe understood as being modified in some instances by the term “about.”Accordingly, in some embodiments, the numerical parameters set forth inthe written description and attached claims are approximations that canvary depending upon the desired properties sought to be obtained by aparticular embodiment. In some embodiments, the numerical parametersshould be construed in light of the number of reported significantdigits and by applying ordinary rounding techniques. Notwithstandingthat the numerical ranges and parameters setting forth the broad scopeof some embodiments of the application are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspracticable.

With the aforementioned preliminary descriptions and definitions inmind, additional background is provided herein below to provide contextfor the genesis and development of the inventive vectors, compositionsand methods described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments are illustrated in the referenced figures. It isintended that the embodiments and figures disclosed herein are to beconsidered illustrative rather than restrictive.

FIG. 1 shows U2OS cells seeded at 1×10⁶ cells per 60 mm dish. Cells wereinfected with KTR27 or KTR27-F at 200 PFU/dish at 72 h post-cell seedingin the presence of tetracycline. KTR27 and KTR27-F plaques werephotographed at 48 and 72 h post-infection.

FIG. 2 shows KTR27-F replication is highly regulated by tetracycline.Vero cells were seeded at 7.5×10⁵ cells per 60 mm dish. At 48 hpost-seeding, triplicate dishes of cells were infected with KTR27 andKTR27-F at a MOI of 1 PFU/cell in a volume of 0.5 ml. After 1.5 h ofincubation at 37° C., the inocula were removed and the cells were washedtwice with acid-glycine saline (to remove membrane-bound extracellularvirions) and then twice by DMEM. KTR27 infections were carried out inthe presence of tetracycline at 2.5 μg/ml, and KTR27-F infections werecarried out in the presence and absence of tetracycline. Infected cellswere harvested at 48 and 72 h post-infection. Viral titers weredetermined on U2OS monolayers in the presence of tetracycline. KTR27-Fproduction in the absence of tetracycline was not detected. Viral titersare expressed as means±standard deviation.

FIGS. 3A and 3B show KTR27-F replication is efficient and highlyregulated in various human tumor cell lines. Human cancer cells H1299(lung), U87 (glioma), MDA MB 231 (breast), and MCF7 (breast) were seededat 7.5×10⁵, 1×10⁶, 7.5×10⁵, and 7.5×10⁵ cells per 60 mm dish,respectively. At 48, 24, 72, and 48 h post-seeding, respectively,triplicate dishes were infected. (FIG. 3A) H1299, U87, MDA-MB-231, andMCF-7 dishes were infected with KTR27 and KTR27-F at a MOI of 1 PFU/cellin a volume of 0.5 ml. After 1.5 h of incubation at 37° C., the inoculawere removed and the cells were washed twice with acid-glycine salineand then twice by DMEM. Infections were then carried out in the absenceor presence of tetracycline at 2.5 μg/ml. Infected cells were harvestedat 48, 72, 72, and 40 h post-infection, respectively, and viral titerswere determined on U2OS monolayers in the presence of tetracycline.Numbers located above the brackets indicate the fold difference in viralyield between the indicated conditions. (FIG. 3B) H1299, U87,MDA-MB-231, and MCF-7 cells were mock-infected and infected with KTR5and KTR27 at MOIs 0.25, 1, 1, and 0.25 PFU/cell, respectively. Cellswere harvested at 72, 72, 96, and 72 h post-infection. Viable cells werecounted by trypan blue exclusion and graphed as a percentage of viablecells in the mock-infected controls, expressed as means±standarddeviation.

FIGS. 4A-4C show cytotoxicity and replication of KTR27-F aresignificantly enhanced in human breast cancer cells versus in normalhuman breast fibroblasts. For results labeled “HF-serum free,” primaryhuman fibroblasts (HF) were seeded at 1.5×10⁶ cells per 60 mm dish innormal growth medium. 24 h post-seeding, normal medium was removed andreplaced with serum-free DMEM containing antibiotics. These cells wereinfected at 42 h post-serum starvation. All other cells were seeded at7.5×10⁵ cells per 60 mm dish in normal growth medium and infected 66 hpost-seeding. All cells described above were either mock infected orinfected with KTR27-F at a MOI of 1 PFU/cell in the absence or presenceof tetracycline at 2.5 μg/ml in DMEM containing 2% FBS. (FIG. 4A)Triplicate dishes of infected cells were harvested at 48 hpost-infection and viral titers were determined on U2OS monolayers inthe presence of tetracycline. (FIG. 4B) Mock-infected and infected cellsin the presence of tetracycline in triplicate dishes were harvested at48 h post-infection. Viable cells were counted by trypan blue exclusionand graphed as a percentage of viable cells in the mock-infectedcontrols, expressed as means±standard deviation. (FIG. 4C) Selectivelysis of MCF7 cells. Images cells infected with KTR27-F in the absenceand presence of tetracycline, photographed at 48 h post-infection.

FIG. 5 shows KTR27-F is avirulent following intracerebral inoculation.Female CD1 mice were intracerebrally inoculated with 20 μl of DMEM orDMEM containing 1×10⁷ PFU of indicated viruses. Half of the miceinjected with KTR27-F were fed a doxycycline-containing diet beginningthree days prior to inoculation (T+). The mice were examined for signsof illness for 29 days.

DESCRIPTION OF THE INVENTION

Oncolytic viruses are genetically modified viruses that preferentiallyreplicate in host cancer cells, leading to the production of newviruses, lysis of cancer cells, and ultimately, induction oftumor-specific immunity. Using the T-REx™ (Invitrogen, CA) gene switchtechnology and a self-cleaving ribozyme, a novel oncolytic HSV-1recombinant, KTR27, was constructed, whose replication can be tightlycontrolled and regulated by tetracycline in a dose-dependent manner.This virus is further described in Yao et al., J Virol, 2010 and U.S.Pat. No. 8,236,941, which are incorporated herein by reference in theirentirety. Infection of normal replicating cells as well as multiplehuman cancer cell types with KTR27 in the presence of tetracycline ledto 1000- to 250,000-fold higher progeny virus production than in theabsence of tetracycline, while little viral replication andvirus-associated cytotoxicity are observed in infected growth-arrestednormal human cells. Importantly, KTR27 is very effective againstpre-established Non-Small cell lung cancer in nude mice and can preventthe growth of pre-established M3 mouse melanoma in immuno-competentmice. Intratumoral inoculation of KTR27 can elicit systemic immuneresponse that can effectively prevent the growth of a distant tumor inimmuno-competent mice.

In an effort to further enhance the therapeutic efficacy of KTR27 andits effectiveness in eliciting tumor specific immunity followingoncolytic virotherapy, a fusogenic variant of KTR27, KTR27-F, wasisolated. Work described herein demonstrate that KTR27-F issignificantly more superior to its non-fusogenic parent in lysingvarious tested human cancer cells. Like KTR27, replication of KTR27-F inprimary human fibroblasts is markedly reduced compared with varioushuman tumor cells. The yield of KTR27-F in human breast cancer cells(MCF-7) is 21,800-fold higher than in growth-arrested normal humanbreast fibroblasts. Moreover, while infection of growth-arrested humanbreast fibroblasts with KTR27-F induced little or no cytotoxicity in theinfected cells, over 99% of infected MCF7 cells were non-viable comparedwith the mock-infected control. Collectively, KTR27-F represents anadvancement in the design of safer and more effective oncolytic viruses.

HSV-1 is a human neurotropic virus that is capable of infectingvirtually all vertebrate cells. Natural infections follow either alytic, replicative cycle or establish latency, usually in peripheralganglia, where the DNA is maintained indefinitely in an episomal state.HSV-1 contains a double-stranded, linear DNA genome, about 152 kilobasesin length, which has been completely sequenced by McGeoch (McGeoch etal., J. Gen. Virol. 69: 1531 (1988); McGeoch et al., Nucleic Acids Res14: 1727 (1986); McGeoch et al., J. Mol. Biol. 181: 1 (1985); Perry andMcGeoch, J. Gen. Virol. 69:2831 (1988); Szpara M L et al., J Virol.2010, 84:5303; Macdonald S J et al., J Virol. 2012, 86:6371). DNAreplication and virion assembly occurs in the nucleus of infected cells.Late in infection, concatemeric viral DNA is cleaved into genome lengthmolecules which are packaged into virions. In the CNS, herpes simplexvirus spreads transneuronally followed by intraaxonal transport to thenucleus, either retrograde or anterograde, where replication occurs.

One aspect described herein provides an oncolytic Herpes Simplex Virus(HSV) comprising recombinant DNA, wherein the recombinant DNA has bothICP0 and ICP34.5 gene product deleted or does not express functionalICP0 and ICP34.5.

Infected cell protein 34.5 (ICP34.5) is a protein (e.g., a gene product)expressed by the γ34.5 gene in viruses, such as the herpes simplexvirus. IPC34.5 has been shown to block the cellar stress response to aviral infection (Agarwalla, P. K., et al. Method in Mol. Bio., 2012).Infected cell polypeptide 0 (ICP0) is a protein encoded by the HSV-1 α0gene. ICP0 is generated during the immediate-early phase of viral geneexpression. ICP0 is synthesized and transported to the nucleus of theinfected host cell, where it promotes transcription from viral genes,disrupts nuclear and cytoplasmic cellular structures, such as themicrotubule network, and alters the expression of host genes.

One skilled in the art can determine if the ICP0 or ICP34.5 geneproducts have been deleted or if the virus does not express functionalforms of these gene products using PCR-based assays to detect thepresence of the gene in the viral genome or the expression of the geneproducts, or using functional assays to assess their function,respectively.

In one embodiment, the gene that encodes these gene products contain amutation, for example, an inactivating mutation, that inhibits properexpression of the gene product. For example, the gene may encode amutation in the gene product that inhibits proper folding, expression,function, ect. of the gene product. As used herein, the term“inactivating mutation” is intended to broadly mean a mutation oralteration to a gene wherein the expression of that gene issignificantly decreased, or wherein the gene product is renderednonfunctional, or its ability to function is significantly decreased.The term “gene” encompasses both the regions coding the gene product aswell as regulatory regions for that gene, such as a promoter orenhancer, unless otherwise indicated.

Ways to achieve such alterations include: (a) any method to disrupt theexpression of the product of the gene or (b) any method to render theexpressed gene nonfunctional. Numerous methods to disrupt the expressionof a gene are known, including the alterations of the coding region ofthe gene, or its promoter sequence, by insertions, deletions and/or basechanges. (See, Roizman, B. and Jenkins, F. J., Science 229: 1208-1214(1985)).

Further described herein is an oncolytic Herpes Simplex Virus (HSV)comprising recombinant DNA, wherein the recombinant DNA comprises: (a) agene comprising a 5′ untranslated region and a HSV-1, or HSV-2, ICP27gene that is operably linked to an ICP27 promoter comprising a TATAelement; (b) a tetracycline operator sequence positioned between 6 and24 nucleotides 3′ to said TATA element, wherein the ICP27 gene lies 3′to said tetracycline operator sequence; (c) a ribozyme sequence locatedin said 5′ untranslated region of said gene; (d) a gene sequenceencoding tetracycline repressor operably linked to an immediate earlypromoter, wherein the gene sequence is located at the ICP0 locus; and(e) a variant gene that increases syncytium formation as compared towild type, wherein the HSV-1, or HSV-2, variant gene is selected fromthe group consisting of: a glycoprotein K (gK) variant; a glycoprotein B(gB) variant; a UL24 variant; and UL20 gene variant, wherein saidoncolytic HSV does not encode functional ICP0 and functional ICP34.5protein. In one embodiment, the recombinant DNA is derived from theHSV-1 genome. In an alternative embodiment, the recombinant DNA isderived from the HSV-2 genome. In one embodiment, the genome of the HSVcomprising recombinant DNA consists of, consists essentially of, orcomprises the sequence of SEQ ID NO: 1. The nucleotide sequence of SEQID NO: 1 contains the plasmid vector sequence present in pSH-tetR (SEQID NO: 9).

An essential feature of the DNA of the present invention is the presenceof a gene needed for virus replication that is operably linked to apromoter having a TATA element. A tet operator sequence is locatedbetween 6 and 24 nucleotides 3′ to the last nucleotide in the TATAelement of the promoter and 5′ to the gene. The strength with which thetet repressor binds to the operator sequence is enhanced by using a formof operator which contains two op2 repressor binding sites (each suchsite having the nucleotide sequence: TCCCTATCAGTGATAGAGA (SEQ ID NO: 8))linked by a sequence of 2-20, preferably 1-3 or 10-13, nucleotides. Whenrepressor is bound to this operator, very little or no transcription ofthe associated gene will occur. If DNA with these characteristics ispresent in a cell that also expresses the tetracycline repressor,transcription of the gene will be blocked by the repressor binding tothe operator and replication of the virus will not occur. However, iftetracycline is introduced, it will bind to the repressor, cause it todissociate from the operator, and virus replication will proceed.

During productive infection, HSV gene expression falls into three majorclasses based on the temporal order of expression: immediate-early (a),early (β), and late (γ), with late genes being further divided into twogroups, γ1 and γ2. The expression of immediate-early genes does notrequire de novo viral protein synthesis and is activated by thevirion-associated protein VP16 together with cellular transcriptionfactors when the viral DNA enters the nucleus. The protein products ofthe immediate-early genes are designated infected cell polypeptidesICP0, ICP4, ICP22, ICP27, and ICP47 and it is the promoters of thesegenes that are preferably used in directing the expression of tetrepressor (tetR). The expression of a gene needed for virus replicationis under the control of the tetO-containing promoters and theseessential genes may be immediate-early, early or late genes, e.g., ICP4,ICP27, ICP8, UL9, gD and VPS. In one embodiment, the tetR has thesequence of SEQ ID NO: 9.

ICP0 plays a major role in enhancing the reactivation of HSV fromlatency and confers a significant growth advantage on the virus at lowmultiplicities of infection. ICP4 is the major transcriptionalregulatory protein of HSV-1, which activates the expression of viralearly and late genes. ICP27 is essential for productive viral infectionand is required for efficient viral DNA replication and the optimalexpression of subset of viral β genes and γ1 genes as well as viral γ2genes. The function of ICP4? during HSV infection appears to be todown-regulate the expression of the major histocompatibility complex(MHC) class I on the surface of infected cells.

The recombinant DNA may also include at least one, and preferably atleast two, sequences coding for the tetracycline repressor withexpression of these sequences being under the control of an immediateearly promoter, preferably ICP0 or ICP4. The sequence for the HSV ICP0and ICP4 promoters and for the genes whose regulation they endogenouslycontrol are well known in the art (Perry, et al., J. Gen. Virol.67:2365-2380 (1986); McGeoch et al., J. Gen. Virol. 72:3057-3075 (1991);McGeoch et al., Nucl. Acid Res. 14:1727-1745 (1986)) and procedures formaking viral vectors containing these elements have been previouslydescribed (see US published application 2005-02665641n one embodiment,the tetR has the sequence of SEQ ID NO: 9.

These promoters are not only very active in promoting gene expression,they are also specifically induced by VP16, a transactivator releasedwhen HSV-1 infects a cell. Thus, transcription from ICP0 promoter isparticularly high when repressor is most needed to shut down virusreplication. Once appropriate DNA constructs have been produced, theymay be incorporated into HSV-1 virus using methods that are well knownin the art. One appropriate procedure is described in US 2005-0266564but other methods known in the art may also be employed.

In various embodiments, the variant gene comprises at least one aminoacid change that deviates from the wild-type sequence of the gene. Inone embodiment, an oncolytic HSV described herein can contain two ormore amino acid substitutions in at least one variant gene. The at leasttwo amino acid substitutions can be found in the same gene, for example,the gK variant gene contains at least two amino acid substitutions.Alternatively, the at least two amino acid substitutions can be found inthe at least two different genes, for example, the gK variant gene andthe UL24 variant gene each contains at least one amino acidsubstitutions.

SEQ ID NO: 2 is the amino acid sequence encoding gK (strain KOS).

(SEQ ID NO: 2) MLAVRSLQHLSTVVLITAYGLVLVWYTVFGASPLHRCIYAVRPTGTNNDTALVWMKMNQTLLFLGAPTHPPNGGWRNHAHICYANLIAGRVVPFQVPPDATNRRIMNVHEAVNCLETLWYTRVRLVVVGWFLYLAFVALHQRRCMFGVVSPAHKMVAPATYLLNYAGRIVSSVFLQYPYTKITRLLCELSVQRQNLVQLFETDPVTFLYHRPAIGVIVGCELMLRFVAVGLIVGTAFISRGACAITYPLFLTITTWCFVSTIGLTELYCILRRGPAPKNADKAAAPGRSKGLSGVCGRCCSIILSGIAMRLCYIAVVAGVVLVALHYEQEIQRRLFDV

SEQ ID NO: 3 is the amino acid sequence encoding UL24 (strain KOS).

(SEQ ID NO: 3) MAARTRSLVERRRVLMAGVRSHTRFYKALAKEVREFHATKICGTLLTLLSGSLQGRSVFEATRVTLICEVDLGPRRPDCICVFEFANDKTLGGVCVIIELKTCKYISSGDTASKREQRATGMKQLRHSLKLLQSLAPPGDKIVYLCPVLVFVAQRTLRVSRVTRLVPQKVSGNITAVVRMLQSLSTYTVPMEPRTQRARRRRGGAARGSASRPKRSHSGARDPPEPAARQVPPADQTPASTEGGGVLKRIAALFC VPVATKTKPRAASE

Exemplary amino acid substitutions present in the variant gene aredescribed in Table 1.

TABLE 1 Amino acid (A.A.) substitution in variant genes. SEQ ID A.A.Wild-type Substitution Gene NO: Position A.A. A.A. gK 2 40 Ala Val gK 240 Ala Val gK 2 99 Asp Asn gK 2 304 Leu Pro gK 2 310 Arg Leu UL24 3 113Ser Asn

In Table 1, “X” refers to any known amino acid. It is specificallycontemplated herein that any amino acid in a variant gene can besubstituted for any known amino acid. The list provided in Table 1 ismeant to be exemplary, and is in no way supposed to be limiting to theinvention. All mutations listed in table 1 for gK are derived from theHSV-1 KOS strain.

The oncolytic HSV described herein comprises a sequence encoding aribozyme. A ribozyme is an RNA molecule that is capable of catalyzing abiochemical reaction in a similar manner as a protein enzyme. Forexample, a ribozyme is commonly known to facilitate cleavage or ligationof RNA and DNA, and peptide bond formation. Ribozymes have further rolesin RNA processing, such as RNA splicing, viral replication, and transferRNA biosynthesis. In one embodiment, the oncolytic HSV described hereinhas a ribozyme sequence that is naturally occurring. In an alternativeembodiment, the oncolytic HSV described herein has a synthetic ribozymesequence, e.g., a non-naturally occurring ribozyme. Ribozymes arefurther described in, e.g., Yen et al., Nature 431:471-476, 2004, thecontents of which are incorporated herein by reference in its entirety.In one embodiment, the ribozyme is N107 ribozyme.

SEQ ID NO: 4 is a nucleotide sequence encoding N107 ribozyme.

(SEQ ID NO: 4) ctgaggtgcaggtacatccagctgacgagtcccaaataggacgaaacgcgcttcggtgtgtcctggattccactgctatcc

In one embodiment, the oncolytic HSV described herein further comprisesat least one polypeptide that encodes a product (e.g., a protein, agene, a gene product, or an antibody or antibody reagent) that canincrease the efficacy of the oncolytic HSV to induce ananti-tumor-specific immunity. Exemplary products include, but are notlimited to, interleukin 2 (IL2), interleukin 12 (IL12), interleukin 15(IL15), an anti-PD-1 antibody or antibody reagent, an anti-PD-L1antibody or antibody reagent, an anti-OX40 antibody or antibody reagent,CTLA-4 antibody or antibody reagent, TIM-3 antibody or antibody reagent,and TIGIT antibody or antibody reagent. In one embodiment, the productis a fragment of IL-2, IL-12, or IL-15, that comprises the samefunctionality of IL-2, IL-12, or IL-15, as described herein below. Oneskilled in the art can determine if an anti-tumor specific immunity isinduced using stand techniques in the art, which are further describedin, for example, Clay, T M, et al. Clinical Cancer Research (2001);Malyguine, A, et al. J Transl Med (2004); or Macchia I, et al. BioMedResearch International (2013), each of which are incorporated herein byreference in their entireties.

Interleukin-2 (IL-2) is an interleukin, a type of cytokine signalingmolecule in the immune system. IL-2 regulates the activities of whiteblood cells (for example, leukocytes and lymphocytes) that areresponsible for immunity. IL-2 is part of the body's natural response tomicrobial infection, and in discriminating between foreign “non-self”and “self”. It mediates its effects by binding to IL-2 receptors, whichare expressed by lymphocytes. Sequences for IL-2, also known TCGF andlympokine, are known for a number of species, e.g., human IL-2 (NCBIGene ID: 3558) polypeptide (e.g., NCBI Ref Seq NP_000577.2) and mRNA(e.g., NCBI Ref Seq NM_000586.3). IL-2 can refer to human IL-2,including naturally occurring variants, molecules, and alleles thereof.IL-2 refers to the mammalian IL-2 of, e.g., mouse, rat, rabbit, dog,cat, cow, horse, pig, and the like. The nucleic sequence of SEQ ID NO: 5comprises the nucleic sequence which encodes IL-2.

SEQ ID NO: 5 is the nucleotide sequence encoding IL-2.

(SEQ ID NO: 5) atgta 61 caggatgcaa ctcctgtctt gcattgcact aagtcttgcacttgtcacaa acagtgcacc 121 tacttcaagt tctacaaaga aaacacagct acaactggagcatttactgc tggatttaca 181 gatgattttg aatggaatta ataattacaa gaatcccaaactcaccagga tgctcacatt 241 taagttttac atgcccaaga aggccacaga actgaaacatcttcagtgtc tagaagaaga 301 actcaaacct ctggaggaag tgctaaattt agctcaaagcaaaaactttc acttaagacc 361 cagggactta atcagcaata tcaacgtaat agttctggaactaaagggat ctgaaacaac 421 attcatgtgt gaatatgctg atgagacagc aaccattgtagaatttctga acagatggat 481 taccttttgt caaagcatca tctcaacact gacttgataa

Interleukin-12 (IL-12) is an interleukin naturally produced by dendriticcells, macrophages, neutrophils, and human B-lymphoblastoid cells(NC-37) in response to antigenic stimulation. IL-12 is involved in thedifferentiation of naive T cells into Th1 cells. It is known as a Tcell-stimulating factor, which can stimulate the growth and function ofT cells. It stimulates the production of interferon-gamma (IFN-γ) andtumor necrosis factor-alpha (TNF-α) from T cells and natural killer (NK)cells, and reduces IL-4 mediated suppression of IFN-γ. Sequences forIL-12a, also known P35, CLMF, NFSK, and KSF1, are known for a number ofspecies, e.g., human IL-12a (NCBI Gene ID: 3592) polypeptide (e.g., NCBIRef Seq NP_000873.2) and mRNA (e.g., NCBI Ref Seq NM_000882.3). IL-12can refer to human IL-12, including naturally occurring variants,molecules, and alleles thereof. IL-12 refers to the mammalian IL-12 of,e.g., mouse, rat, rabbit, dog, cat, cow, horse, pig, and the like. Thenucleic sequence of SEQ ID NO:6 comprises the nucleic sequence whichencodes IL-12a.

SEQ ID NO: 6 is the nucleotide sequence encoding IL-12a.

(SEQ ID NO: 6) aatgtggccc cctgggtcag 241cctcccagcc accgccctca cctgccgcgg ccacaggtct gcatccagcg gctcgccctg 301tgtccctgca gtgccggctc agcatgtgtc cagcgcgcag cctcctcctt gtggctaccc 361tggtcctcct ggaccacctc agtttggcca gaaacctccc cgtggccact ccagacccag 421gaatgttccc atgccttcac cactcccaaa acctgctgag ggccgtcagc aacatgctcc 481agaaggccag acaaactcta gaattttacc cttgcacttc tgaagagatt gatcatgaag 541atatcacaaa agataaaacc agcacagtgg aggcctgttt accattggaa ttaaccaaga 601atgagagttg cctaaattcc agagagacct ctttcataac taatgggagt tgcctggcct 661ccagaaagac ctcttttatg atggccctgt gccttagtag tatttatgaa gacttgaaga 721tgtaccaggt ggagttcaag accatgaatg caaagcttct gatggatcct aagaggcaga 781tctttctaga tcaaaacatg ctggcagtta ttgatgagct gatgcaggcc ctgaatttca 841acagtgagac tgtgccacaa aaatcctccc ttgaagaacc ggatttttat aaaactaaaa 901tcaagctctg catacttctt catgctttca gaattcgggc agtgactatt gatagagtga 961tgagctatct gaatgcttcc taa

Interleukin-15 (IL-15) is an interleukin secreted by mononuclearphagocytes (and some other cells) following infection by virus(es). Thiscytokine induces cell proliferation of natural killer cells; cells ofthe innate immune system whose principal role is to kill virallyinfected cells. Sequences for IL-15 are known for a number of species,e.g., human IL-15 (NCBI Gene ID: 3600) polypeptide (e.g., NCBI Ref SeqNP_000585.4) and mRNA (e.g., NCBI Ref Seq NM_000576.1). IL-15 can referto human IL-15, including naturally occurring variants, molecules, andalleles thereof. IL-15 refers to the mammalian IL-15 of, e.g., mouse,rat, rabbit, dog, cat, cow, horse, pig, and the like. The nucleicsequence of SEQ ID NO: 7 comprises the nucleic sequence which encodesIL-15.

SEQ ID NO: 7 is the nucleotide sequence encoding IL-15.

(SEQ ID NO: 7) atgaga atttcgaaac cacatttgag aagtatttcc atccagtgct 421acttgtgttt acttctaaac agtcattttc taactgaagc tggcattcat gtcttcattt 481tgggctgttt cagtgcaggg cttcctaaaa cagaagccaa ctgggtgaat gtaataagtg 541atttgaaaaa aattgaagat cttattcaat ctatgcatat tgatgctact ttatatacgg 601aaagtgatgt tcaccccagt tgcaaagtaa cagcaatgaa gtgctttctc ttggagttac 661aagttatttc acttgagtcc ggagatgcaa gtattcatga tacagtagaa aatctgatca 721tcctagcaaa caacagtttg tcttctaatg ggaatgtaac agaatctgga tgcaaagaat 781gtgaggaact ggaggaaaaa aatattaaag aatttttgca gagttttgta catattgtcc 841aaatgttcat caacacttct tga

Antibodies or antibody reagents that bind to PD-1, or its ligand PD-L1,are described in U.S. Pat. Nos. 7,488,802; 7,943,743; 8,008,449;8,168,757; 8,217,149, and PCT Published Patent Application Nos:WO03042402, WO2008156712, WO2010089411, WO2010036959, WO2011066342,WO2011159877, WO2011082400, and WO2011161699; which are incorporated byreference herein in their entireties. In certain embodiments the PD-1antibodies include nivolumab (MDX 1106, BMS 936558, ONO 4538), a fullyhuman IgG4 antibody that binds to and blocks the activation of PD-1 byits ligands PD-L1 and PD-L2; lambrolizumab (MK-3475 or SCH 900475), ahumanized monoclonal IgG4 antibody against PD-1; CT-011 a humanizedantibody that binds PD-1; AMP-224, a fusion protein of B7-DC; anantibody Fc portion; BMS-936559 (MDX-1105-01) for PD-L1 (B7-H1)blockade. Also specifically contemplated herein are agents that disruptor block the interaction between PD-1 and PD-L1, such as a high affinityPD-L1 antagonist.

Non-limiting examples of PD-1 antibodies include: pembrolizumab (Merck);nivolumab (Bristol Meyers Squibb); pidilizumab (Medivation); and AUNP12(Aurigene). Non-limiting examples of PD-L1 antibodies can includeatezolizumab (Genentech); MPDL3280A (Roche); MEDI4736 (AstraZeneca);MSB0010718C (EMD Serono); avelumab (Merck); and durvalumab (Medimmune).

Antibodies that bind to OX40 (also known as CD134), are described in USpatent Nos. U.S. Pat. Nos. 9,006,399, 9,738,723, 9,975,957, 9,969,810,9,828,432; PCT Published Patent Application Nos: WO2015153513,WO2014148895, WO2017021791, WO2018002339; and US application Nos:US20180273632; US20180237534; US20180230227; US20120269825; which areincorporated by reference herein in their entireties.

Antibodies that bind to CTLA-4, are described in US patent Nos. U.S.Pat. Nos. 9,714,290, 6,984,720, 7,605,238, 6,682,736 U.S. Pat. No.7,452,535; PCT Published Patent Application No: WO2009100140; and USapplication Nos: US20090117132A, US20030086930, US20050226875,US20090238820; which are incorporated by reference herein in theirentireties.

Non-limiting examples of CTLA-4 antibodies include: ipilimumab(Bristol-Myers Squibb)

Antibodies that bind to TIM3, are described in US patent Nos. U.S. Pat.Nos. 8,552,156, 9,605,070, 9,163,087, 8,329,660; PCT Published PatentApplication No: WO2018036561, WO2017031242, WO2017178493; and USapplication Nos: US20170306016, US20150110792, US20180057591,US20160200815; which are incorporated by reference herein in theirentireties.

Antibodies that bind to TIGIT (also known as CD134), are described in USpatent Nos. U.S. Ser. No. 10/017,572, U.S. Pat. No. 9,713,641; PCTPublished Patent Application No: WO2017030823; and US application Nos:US20160355589, US20160176963, US20150322119; which are incorporated byreference herein in their entireties.

One aspect of the invention described herein provides a compositioncomprising any of the oncolytic HSV described herein. In one embodiment,the composition is a pharmaceutical composition. As used herein, theterm “pharmaceutical composition” refers to the active agent incombination with a pharmaceutically acceptable carrier e.g. a carriercommonly used in the pharmaceutical industry.

In one embodiment, the composition further comprises at least onepharmaceutically acceptable carrier. Pharmaceutically acceptablecarriers are well known in the art and include aqueous solutions such asphysiologically buffered saline or other solvents or vehicles such asglycols, glycerol, vegetable oils (e.g., olive oil) or injectableorganic esters. A pharmaceutically acceptable carrier can be used toadminister the compositions of the invention to a cell in vitro or to asubject in vivo. A pharmaceutically acceptable carrier can contain aphysiologically acceptable compound that acts, for example, to stabilizethe composition or to increase the absorption of the agent. Aphysiologically acceptable compound can include, for example,carbohydrates, such as glucose, sucrose or dextrans, antioxidants, suchas ascorbic acid or glutathione, chelating agents, low molecular weightproteins or other stabilizers or excipients.

Other physiologically acceptable compounds include wetting agents,emulsifying agents, dispersing agents or preservatives, which areparticularly useful for preventing the growth or action ofmicroorganisms. Various preservatives are well known and include, forexample, phenol and ascorbic acid. One skilled in the art would knowthat the choice of a pharmaceutically acceptable carrier, including aphysiologically acceptable compound, depends, for example, on the routeof administration of the oncolytic HSV.

The oncolytic viruses described herein or composition thereof can beadministered to a subject having cancer. In one embodiment, an agentthat regulates the tet operator is further administered with theoncolytic viruses described herein or composition thereof. Exemplaryagents include, but are not limited to, doxycycline or tetracycline.

In one embodiment, the cancer is a solid tumor. The solid tumor can bemalignant or benign. In one embodiment, the subject is diagnosed or hasbeen diagnosed with having a carcinoma, a melanoma, a sarcoma, a germcell tumor, and a blastoma. Exemplary cancers include, but are in no waylimited to, non-small-cell lung cancer, breast cancer, brain cancer,colon cancer, prostate cancer, liver cancer, lung cancer, ovariancancer, skin cancer, and pancreatic cancer. In one embodiment, thecancer is metastatic. These types of cancers are known in the art andcan be diagnosed by a skilled clinician using standard techniques knownin the art, for example blood analysis, blood cell count analysis,tissue biopsy non-invasive imaging, and review of family history.

In cases where tumors are readily accessible, e.g., tumors of the skin,mouth or which are accessible as the result of surgery, virus can beapplied topically. In other cases, it can be administered by injectionor infusion. The agent that regulates the tet operator, for exampledoxycycline or tetracycline, used prior to infection or at a time ofinfection can also be administered in this way or it can be administeredsystemically.

Although certain routes of administration are provided in the foregoingdescription, according to the invention, any suitable route ofadministration of the vectors may be adapted, and therefore the routesof administration described above are not intended to be limiting.Routes of administration may including but are not limited to,intravenous, oral, buccal, intranasal, inhalation, topical applicationto a mucosal membrane or injection, including intratumoral, intradermal,intrathecal, intracisternal, intralesional or any other type ofinjection. Administration can be effected continuously or intermittentlyand will vary with the subject and the condition to be treated. One ofskill in the art would readily appreciate that the various routes ofadministration described herein would allow for the inventive vectors orcompositions to be delivered on, in, or near the tumor or targetedcancer cells. One of skill in the art would also readily appreciate thatvarious routes of administration described herein will allow for thevectors and compositions described herein to be delivered to a region inthe vicinity of the tumor or individual cells to be treated. “In thevicinity” can include any tissue or bodily fluid in the subject that isin sufficiently close proximity to the tumor or individual cancer cellssuch that at least a portion of the vectors or compositions administeredto the subject reach their intended targets and exert their therapeuticeffects.

Prior to administration, the oncolytic viruses can be suspended in anypharmaceutically acceptable solution including sterile isotonic saline,water, phosphate buffered saline, 1,2-propylene glycol, polyglycolsmixed with water, Ringer's solution, etc. The exact number of viruses tobe administered is not crucial to the invention but should be an“effective amount,” i.e., an amount sufficient to cause cell lysisextensive enough to generate an immune response to released tumorantigens. Since virus is replicated in the cells after infection, thenumber initially administered will increase rapidly with time. Thus,widely different amounts of initially administered virus can give thesame result by varying the time that they are allowed to replicate,i.e., the time during which cells are exposed to tetracycline. Ingeneral, it is expected that the number of viruses (PFU) initiallyadministered will be between 1×10⁶ and 1×10¹⁰.

Tetracycline or doxycycline will be administered either locally orsystemically to induce viral replication at a time of infection or 1-72h prior to infection. The amount of tetracycline or doxycycline to beadministered will depend upon the route of delivery. In vitro, 1 μg/mlof tetracycline is more than sufficient to allow viral replication ininfected cells. Thus, when delivered locally, a solution containinganywhere from 0.01 μg/ml to 100 μg/ml may be administered. However, muchhigher doses of tetracycline or doxycycline (e.g., 10-500 mg/ml) can beemployed if desired. The total amount given locally at a single timewill depend on the size of the tumor or tumors undergoing treatment butin general, it is expected that between 0.5 and 200 ml of tetracyclinesolution would be used at a time. When given systemically, higher dosesof tetracycline will be given but it is expected that the total amountneeded will be significantly less than that typically used to treatbacterial infections (usually 1-2 grams per day in adults divided into2-4 equal doses and, in children, 10-20 mg per pound of body weight perday). It is expected that 100-200 mg per day should be effective in mostcases.

The effectiveness of a dosage, as well as the effectiveness of theoverall treatment can be assessed by monitoring tumor size usingstandard imaging techniques over a period of days, weeks and/or months.A shrinkage in the size or number of tumors is an indication that thetreatment has been successful. If this does not occur or continue, thenthe treatment can be repeated as many times as desired. In addition,treatment with virus can be combined with any other therapy typicallyused for solid tumors, including surgery, radiation therapy orchemotherapy. In addition, the procedure can be combined with methods orcompositions designed to help induce an immune response.

As used herein, the term “therapeutically effective amount” is intendedto mean the amount of vector which exerts oncolytic activity, causingattenuation or inhibition of tumor cell proliferation, leading to tumorregression. An effective amount will vary, depending upon the pathologyor condition to be treated, by the patient and his or her status, andother factors well known to those of skill in the art. Effective amountsare easily determined by those of skill in the art. In some embodimentsa therapeutic range is from 10³ to 10¹² plaque forming units introducedonce. In some embodiments a therapeutic dose in the aforementionedtherapeutic range is administered at an interval from every day to everymonth via the intratumoral, intrathecal, convection-enhanced,intravenous or intra-arterial route.

The invention provided herein can further be described in the followingnumbered paragraphs:

-   -   1. An oncolytic Herpes Simplex Virus (HSV) comprising        recombinant DNA, wherein the recombinant DNA has both ICP0 and        ICP34.5 gene product deleted or does not express functional ICP0        and ICP34.5 gene product.    -   2. An oncolytic Herpes Simplex Virus (HSV) comprising        recombinant DNA, wherein the recombinant DNA comprises:        -   a) a gene comprising a 5′ untranslated region and a HSV-1,            or HSV-2, ICP27 gene that is operably linked to an ICP27            promoter comprising a TATA element;        -   b) a tetracycline operator sequence positioned between 6 and            24 nucleotides 3′ to said TATA element, wherein the ICP27            gene lies 3′ to said tetracycline operator sequence;        -   c) a ribozyme sequence located in said 5′ untranslated            region of said gene;        -   d) a gene sequence encoding tetracycline repressor operably            linked to an HSV immediate-early promoter, wherein the gene            sequence is located at the ICP0 locus; and        -   e) a variant gene that increases syncytium formation as            compared to wild type, wherein the HSV-1, or HSV-2, variant            gene is selected from the group consisting of: a            glycoprotein K (gK) variant; a glycoprotein B (gB) variant;            a UL24 variant; and UL20 gene variant,    -   wherein said oncolytic HSV does not encode functional ICP0 and        functional ICP34.5 protein.    -   3. The oncolytic HSV of paragraph 2, wherein the variant gene is        a gK variant gene that encodes an amino acid substitution        selected from the group consisting of: an Ala to Val amino acid        substitution corresponding to amino acid 40 of SEQ ID NO: 2; an        Ala to “x” amino acid substitution corresponding to amino acid        40 of SEQ ID NO: 2, wherein “x” is any amino acid; an Asp to Asn        amino acid substitution corresponding to amino acid 99 of SEQ ID        NO: 2; a Leu to Pro amino acid substitution corresponding to        amino acid 304 of SEQ ID NO: 2; and an Arg to Leu amino acid        substitution corresponding to amino acid 310 of SEQ ID NO: 2.    -   4. The oncolytic HSV of any preceding paragraph, wherein the        variant gene is a UL24 gene that encodes a Ser to Asn amino acid        substitution corresponding to amino acid 113 of SEQ ID NO: 3.    -   5. The oncolytic HSV of any preceding paragraph, further        comprising a variant UL24 gene that encodes a Ser to Asn amino        acid substitution corresponding to amino acid 113 of SEQ ID NO:        3.    -   6. The oncolytic HSV of any preceding paragraph, wherein the        tetracycline operator sequence comprises two Op2 repressor        binding sites.    -   7. The oncolytic HSV of any preceding paragraph, wherein the        ICP27 promoter is an HSV-1 or HSV-2 ICP27 promoter.    -   8. The oncolytic HSV of any preceding paragraph, wherein the        immediate-early promoter is an HSV-1 or HSV-2 immediate-early        promoter.    -   9. The oncolytic HSV of any preceding paragraph, wherein the HSV        immediate-early promoter is selected from the group consisting        of: ICP0 promoter and ICP4 promoter.    -   10. The oncolytic HSV of any preceding paragraph, wherein the        recombinant DNA is part of the HSV-1 genome.    -   11. The oncolytic HSV of any preceding paragraph, wherein the        recombinant DNA is part of the HSV-2 genome.    -   12. The oncolytic HSV of any preceding paragraph, further        comprising a pharmaceutically acceptable carrier.    -   13. The oncolytic HSV of any preceding paragraph, further        encoding at least one polypeptide that can increase the efficacy        of the oncolytic HSV to induce an anti-tumor-specific immunity.    -   14. The oncolytic HSV of any preceding paragraph, wherein the at        least one polypeptide encodes a product selected from the group        consisting of: interleukin 2 (IL2), interleukin 12 (IL12),        interleukin 15 (IL15), an anti-PD-1 antibody or antibody        reagent, an anti-PD-L1 antibody or antibody reagent, an        anti-OX40 antibody or antibody reagent, CTLA-4 antibody or        antibody reagent, TIM-3 antibody or antibody reagent, and TIGIT        antibody or antibody reagent.    -   15. A composition comprising an oncolytic HSV of any preceding        paragraph.    -   16. The composition of any preceding paragraph, further        comprising a pharmaceutically acceptable carrier.    -   17. A method for treating cancer, the method comprising        administering the oncolytic HSV of any preceding paragraph or        the composition of any preceding paragraph to a subject having        cancer.    -   18. The method of any preceding paragraph, wherein the cancer is        a solid tumor.    -   19. The method of any preceding paragraph, wherein the tumor is        benign or malignant.    -   20. The method of any preceding paragraph, wherein the subject        is diagnosed or has been diagnosed as having cancer is selected        from the list consisting of: a carcinoma, a melanoma, a sarcoma,        a germ cell tumor, and a blastoma.    -   21. The method of any preceding paragraph, wherein the subject        is diagnosed or has been diagnosed as having a cancer selected        from the group consisting of: non-small-cell lung cancer, breast        cancer, brain cancer, colon cancer, prostate cancer, liver        cancer, lung cancer, ovarian cancer, skin cancer, and pancreatic        cancer.    -   22. The method of any preceding paragraph, wherein the cancer is        metastatic.    -   23. The method of any preceding paragraph, further comprising        administering an agent that regulates the tet        operator-containing promoter.    -   24. The method of any preceding paragraph, wherein the agent is        doxycycline or tetracycline.    -   25. The method of any preceding paragraph, wherein the agent is        administered locally or systemically.    -   26. The method of any preceding paragraph, wherein the oncolytic        virus is administered directly to the tumor.

EXAMPLES

HSV replicates in epithelial cells and fibroblasts and establisheslife-long latent infection in neuronal cell bodies within the sensoryganglia of infected individuals. During productive infection, HSV genesfall into three major classes based on the temporal order of theirexpression: immediate-early (IE), early (E), and late (L) (Roizman,2001). The HSV-1 viral proteins directly relevant to the current studyare two IE regulatory proteins, ICP27 and ICP0. ICP27 is an essentialviral IE protein that modifies and transports viral transcripts to thecytoplasm (Sandri-Goldin, 2008). Although not essential for productiveinfection, ICP0 is required for efficient viral gene expression andreplication at low multiplicities of infection in normal cells andefficient reactivation from latent infection (Cai and Schaffer, 1989;Leib et al., 1989; Yao and Schaffer, 1995). Studies have revealed thatICP0 is needed to stimulate translation of viral mRNA in quiescent cells(Walsh and Mohr, 2004) and plays a key role in blocking IFN-inducedinhibition of viral infection (Eidson et al., 2002; Mossman et al.,2000). ICP0 also has E3 ubiquitin ligase activity and induces thedisruption and degradation of ND10 proteins that have been implicated incontrolling cell senescence and DNA repair (Everett, 2006). Given thattumor cells are impaired in various cellular pathways, such as DNArepair, interferon signaling, and translation regulation (Kastan andBartek, 2004; Mohr, 2005), it is not surprising that ICP0 deletionmutants replicate more efficiently in cancer cells than in normal cells,in particular, quiescent cells and terminally differentiated cells. Theoncolytic potential of ICP0 mutants was first illustrated by Yao andSchaffer (Yao and Schaffer, 1995), who showed that the plaque-formingefficiency of an ICP0 null mutant in human osteosarcoma cells (U2OS) is100- to 200-fold higher than in non tumorigenic African green monkeykidney cells (Vero). The preferential ability of ICP0 mutants toreplicate in selected types of cancer cells has been further explored inthe recent study of Hummel et al. with an HSV-1 virus lacking both ICP0and HSV-1 virion-associated transactivator, VP16 (Hummel et al., 2005).

Using the T-REx™ (Invitrogen, CA) gene switch technology and aself-cleaving ribozyme, a novel regulatable oncolytic HSV-1 recombinant,KTR27, which encodes the tetR gene controlled by the ICP0 promoter atthe ICP0 locus and the essential ICP27 gene under control of thetetO-bearing ICP27 promoter was constructed (Yao et al., 2010).Infection of normal replicating cells as well as multiple human cancercell types with KTR27 in the presence of tetracycline led to 1000- to250,000-fold higher progeny virus production than in the absence oftetracycline, while little viral replication and virus-associatedcytotoxicity are observed in infected growth-arrested normal humancells. Intratumoral inoculation with KTR27 was shown to markedly inhibittumor growth in a xenograft model of human non-small-cell lung cancer innude mice. It was shown further that replication of KTR27 in theinoculated tumors can be efficiently controlled by local co-delivery oftetracycline to the target tumors at the time of KTR27 inoculation.Collectively, KTR27 possesses a unique pharmacological feature that canlimit its replication to the targeted tumor microenvironment withlocalized tetracycline delivery, thus minimizing unwanted viralreplication in distant tissues following local virotherapy. Thisregulatory mechanism would also allow the replication of the virus to bequickly shut down should adverse effects be detected.

Human cancers are heterogeneous and contain multiple barriers that limitviruses from efficiently infecting distant tumor cells following initialviral replication (McKee et al., 2006; Nagano et al., 2008; Pluen etal., 2001). In an effort to overcome the inability of oncolytic virusesor viral vectors to infect or deliver therapeutic gene to large numberof tumor cells within the tumor mass, a viral fusogenic glycoproteinapproach has been employed. It was specifically contemplated that afusogenic variant of KTR27 could offer a significant immunologicalbenefit in augmenting the anti-tumor response induced by KTR27.

HSV encodes several surface glycoproteins that involve the fusion of theviral envelope with the cell membrane as well as the fusion of aninfected cell with adjacent cells, leading to syncytia. HSV variantsexhibiting extensive syncytium formation consisting of as many asthousands of nuclei can be isolated by the propagation of virus in cellcultures (Pertel and Spear, 1996). Studies have shown that mutations inthe cytoplasmic domain of HSV-1 glycoprotein B (gB) can lead toextensive syncytial (Baghian A et al., J Virol. 67:2396-2401, 1993; BzikD J et al., Virology 137:185-190, 1984; Cai W H et al., J Virol62:2596-2604, 1988; Engel J P et al., Virology 192:112-120, 1993;Diakidi-Kosta A et al., Gage P J et al., J Virol 67:2191-2201, 1993;Virus Res 93-99-108, 2003). HSV-1 syncytial mutations have also beenidentified in gene encoding for glycoprotein K (gK) (Bond V C et al., JGen Virol 61:245-254, 1982; Bond V C and Person S, Virology 132:368-376,1984; Debroy C et al., et al., Virology 145:36-48, 1985; Hutchinson etal., J Virol 66:5603-5609; Pogue-Geile K L et al., Virology 136:100-109,1984; Pogue-Geile K L et al., Virology 157:67-74, 1987), the UL20 gene(Melancon J M et al., J Virol 78:7329-7343, 2004) and the UL24 gene(Sanders P G et al., J Gen Virol 63:277-95, 1982; Jacobson J G et al., JVirol 63:1839-1843; Jacobson J G et al., Virology 242:161-169, 1998).Notably, UL20 interacts with both gB and gK (Foster T P et al., J Virol82:6310-6323, 2008; Chouljenko V N et al., J Virol 84:8596-8606).

During the propagation of KTR27 in U2OS cells, the presence of fusogenicforms of KTR27 was noticed in addition to the non-fusogenic regularKTR27 in passage 3 KTR27 stock. KTR27-F was a second-roundplaque-purified syncytium-forming KTR27 variant (KTR27-F) with a plaquesize ˜12 times larger than that of parental KTR27 and exhibited similarreplication efficiency as KTR27 in U2OS cells. While the replicationefficiency of KTR27-F and KTR27 is comparable in the tested varioushuman cancer cell lines, it was shown that KTR27-F exhibits morestringent tet-dependent regulation in these cells lines withregulatability ranges from ˜65,000-fold to ˜881,000-fold, whereas thedegrees of KTR27 regulation ranged from ˜785-fold to ˜37,000-fold. Theeffectiveness of KTR27-F in killing tested human lung and breast tumorcell lines is enhanced 11 to 37-fold at a low multiplicity of infection.

Sequence analyses of KTR27-F genome confirms that KTR27-F encodes tetRat the HSV-1 ICP0 locus, and ICP27 under the control of thetetO-containing ICP27 promoter with a self-cleaving ribozyme present atthe 5′ untranslated region of ICP27 gene. Using the parental wild-typeHSV-1 strain KOS genome as the reference, a single amino acidsubstitution, Ala to Val at residue 40, is identified in the gK gene ofKTR27-F, while no mutation is found in the gB gene and the UL20 gene.KTR27-F also contains a single amino acid substitution, Ser to Asn atthe residue 113 in UL24 gene. Because the same Ala to Val substitutionhas been identified in the HSV-1 syncytial mutants, syn102, syn105 andsyn 33 (Dolter K E et al., J Virol 68:8277-8281, 1994), which wereisolated from KOS-infected cells in the presence of mutagens,2-aminopurine (Bond V C et al., J Gen Virol 61:245-254, 1982) or5-bromodeoxyuridine (Read G S et al., J Virol 35:105-113, 1980), it isspecifically contemplated that the Ala to Val substitution at residue 40of the gK gene in KTR27-F is a key factor for the observed fusogenicphenotype. Previous studies identified several additional syncytialmutations in the gK gene, which include Ala to Thr at residue 40 insyn20, Asp to Asn at residue 99 in syn31 and syn32, Leu to Pro atresidue 304 in syn30, and Arg to Leu at residue 310 (Dolter K E et al.,J Virol 68:8277-8281, 1994). Whether the Ser to Asn substitution atresidue 113 in the UL24 gene contributes to the fusogenic activity ofKTR27-F remains to be determined.

Surprisingly, sequencing analysis indicates that KTR27-F does not encodethe HSV-1 ICP34.5 gene. Like ICP0, the ICP34.5 gene is located in theinverted repeat region that flanks the unique long region of the HSV-1genome. PCR analyses with primers specific for the ICP34.5 gene indicatethat the ICP34.5 gene is likely non-specifically lost during theconstruction of K0R27-lacZ, the parental virus of KTR27.

Materials and Methods

Cells and Viruses

The osteosarcoma line U2OS and the African green monkey kidney cell line(Vero) were grown in Dulbecco's modified Eagle's medium (DMEM)supplemented with 10% fetal bovine serum (FBS) (Yao and Schaffer, 1995).U2OS cells express a cellular activity that can effectively complementthe function of the HSV-1 IE regulatory protein ICP0 lacking inICP0-mutant viruses (Yao and Schaffer, 1995). Primary human fibroblastswere grown in DMEM containing 10% FBS plus 1×non-essential amino acids(Yao and Eriksson, 1999).

Human non-small-cell lung cancer cells (H1299), human breast cancercells (MCF7), human prostate cancer cells (PC1435), and pancreaticcancer cells (Panc 1) were cultured in DMEM containing 10% FBS. PC1435and MCF7 were kindly provided by Dr. Sheng Xiao (Brigham and Women'sHospital). Panc 1 was the kind gift of Dr. Edward Hwang (Brigham andWomen's Hospital).

7134 is an ICP0-null mutant derived from HSV-1 strain KOS, in which bothcopies of the ICP0 coding sequence are replaced by the LacZ gene ofEscherichia coli (Cai and Schaffer, 1989). 7134 was propagated andassayed in U2OS cells (Yao and Schaffer, 1995). K0R is an HSV-1recombinant generated by recombinational replacement of the LacZ gene in7134 with the DNA sequence encoding tetR (Yao et al., 2006). K0R27-lacZwas derived from K0R in which the ICP27 coding sequence was replacedwith the LacZ gene by homologous recombination (Yao et al., 2010). KTR27is a 7134-derived recombinant virus that encodes tetR under the controlof HSV-1 ICP0 promoter at the ICP0 locus, and the essential ICP27 geneunder the control of the tetO-containing ICP27 promoter and aself-cleaving ribozyme located at the 5′ untranslated region of ICP27coding sequence (Yao et al., J Virol, 2010) (U.S. Pat. No. 8,236,941).

Neurovirulence of KTR27-F

A mouse model for the evaluation of the neurovirulence of KTR27-F wasestablished by injecting 4-6 week female CD1 outbred mice (Charles RiverLaboratories, Wilmington, Mass.) with 20 μl of medium containing 1×10⁷PFU of KTR27-F or 7134. Intracerebral inoculation was performed with a28½ gauge needle with a needle guard such that the distance from theguard to the needle tip was 5.5 mm, and to the beginning of the bevel ofthe needle was 4.5 mm. The needle was inserted at a point equidistantbetween the outer canthus of the eye, the front of the pinna, andmidline of the head (Lynas et al., 1993). Half of the mice inoculatedwith KTR27-F were given a normal diet, and the other half were fed adoxycycline-containing diet at 200 mg/kg (Bio-Serv, Frenchtown, N.J.),beginning 3 days prior to inoculation and lasting for the duration ofthe experiment. Mice were examined for signs of illness for 29 daysfollowing inoculation.

All mouse studies were conducted in accordance with the protocols setforth by the Harvard Medical Area Standing Committee on Animals and theAmerican Veterinary Medical Association. The Harvard Medical Schoolanimal management program is accredited by the Association forAssessment and Accreditation of Laboratory Animal Care (AAALAC) andmeets National Institutes of Health standards as set forth in “The Guidefor the Care and Use of Laboratory Animals” (National Academy Press,1996).

Illumina Sequencing

KTR27-F viral DNA was prepared from KTR27-F-infected U2OS cells withQiagen Genomic DNA kit. Quantitative real-time PCR analysis revealsclose to 55% of total DNA represents KTR27F viral DNA. The isolated DNA(2.2 μg) was used for library construction with TruSeq DNA OCR-FreeLibrary Preparation Kits at Translational Genomics Core Facility,Partners HealthCare, Cambrige, Mass., targeting 550 bp fragments, andwere sequenced on a 250 bp MiSeq run. The resulting contigs wereassembled and analyzed in Illumina MiSeq Reporter Resequencing workflowusing HSV-1 strain KOS genome as the reference.

Results

Selection of KTR27-F. During the propagation of KTR27 in U2OS cells, thepresence of fusogenic forms of KTR27 was noticed in addition to thenon-fusogenic regular KTR27 in passage 3 KTR27 stock. To isolatefusogenic variants of KTR27, passage 3 KTR27 was diluted with DMEMcontaining 10% FBS followed by plaque purification. Specifically, 10×100mm dishes of confluent 72 h-old U2OS cells were infected with thediluted passage 3 KTR27 at either 100 PFU/dish or 200 PFU/dish. After 1h incubation at 37 C, inoculation medium was removed and 10 ml/dish ofDMEM growth medium containing tetracycline at 10 μg/ml were added toeach dish. After an additional 3 h incubation at 37 C,tetracycline-containing medium was removed from individual dishesfollowed by addition of 1 ml/dish of fresh tetracycline-containing DMEMgrowth medium, Infected cells were then overlaid with 1% methylcelluloseprepared in DMEM containing 5% FBS at 25 ml/dish. After incubation at 37C for 72 h, infected dishes were stained with 10 ml/dish of 0.02%neutral-red prepared in DMEM. Individual single fusogenic plaques werepicked at 20 h post neutral-red staining and suspended in 1.5 ml of DMEMgrowth medium followed by amplification in U2OS cells in the presence oftetracycline. KTR27-F was a second-round plaque-purifiedsyncytium-forming KTR27 variant with a plaque size ˜12-13 times largerthan that of parental KTR27 at 48 and 72 h post-infection (FIG. 1),while exhibited similar replication efficiency as KTR27 in U2OS cells.

Control of KTR27-F replication by tetracycline. To assess the dependenceof KTR27-F replication on the presence of tetracycline, Vero cells wereinfected with KTR27-F at a MOI of 1 PFU/cell in the presence and absenceof tetracycline and the infected cells were harvested at 48 and 72 hpost-infection (FIG. 2). While the yield of KTR27-F at 72 hpost-infection was 1.26×10⁶ PFU/ml, no infectious KTR27-F was detectablein cells infected in the absence of tetracycline at either time point,indicating that the regulation of KTR27-F viral replication bytetracycline is greater than 1,260,000-fold in Vero cells.

Tetracycline-dependent replication of KTR27-F in cultured human tumorcells and primary cells. Having demonstrated that the replication ofKTR27-F is as productive as that of KTR27 in Vero cells, and thatKTR27-F is unable to replicate in Vero cells in the absence oftetracycline, the replicative and regulative abilities of KTR27-F invarious human tumor cell lines were then investigated. As a control,KTR27 was also used in these experiments. As depicted in FIG. 3A,KTR27-F infection of human lung, brain, and breast tumor cell linesdemonstrated that KTR27-F regulatability ranges from 52,000-fold to880,000-fold, whereas the degrees of KTR27 regulation ranged from˜785-fold to 37,000-fold. The enhanced regulatability of KTR27-Frelative to that of KTR27 is a combination of slightly increased viralyields in the presence of tetracycline and significantly reduced yieldsin the absence of tetracycline.

The drastic enhancement of the cytotoxic effect of KTR27-F relative tothat of KTR27 is best visualized by the cytotoxicity assays depicted inFIG. 3B. In the human cancer cell lines H1299, U87, MDA-MB-231, andMCF-7, cell death following KTR27-F infection in the presence oftetracycline was ˜11-fold, ˜2.3-fold, ˜28-fold, and ˜37-fold higher,respectively, than cell death following KTR27 infection in the presenceof tetracycline. To directly examine the oncoselectivity of KTR27-F innon-tumor primary human cells relative to a cancer line of similartissue type, MCF-7 cells and dividing and non-dividing human breastfibroblasts were infected with KTR27-F in the presence and absence oftetracycline as described by Yao et al. (2010). The results of FIG. 4Ademonstrate that replication of KTR27-F in primary human fibroblasts,particularly non-dividing fibroblasts, is reduced compared withreplication in MCF-7. Yields of KTR27-F at 72 h post-infection in MCF7cells were approximately 21,800-fold higher than those in theserum-starved fibroblasts, and 1,530-fold higher than in fibroblastsgrown in normal growth medium. Additionally, the cytotoxic effect ofKTR27-F infection in the presence of tetracycline was evaluated (FIG.4B). The results show that KTR27-F exhibits little cytotoxic effect innon-dividing fibroblasts, modest cytotoxic effect in dividingfibroblasts (88% of infected cells remained viable), and drasticcytotoxic effect in MCF-7 cells (0.8% of infected cells remainedviable). The corresponding morphological images of cells from thecytotoxicity assay (FIG. 4C) depict this cytopathic effect in MCF-7(note the extensive formation of syncytia). In contrast, very little orno cytotoxic effects are visible among the infected or mock-infectedhuman fibroblasts. Together, the results presented in FIGS. 4A and 4Bindicate that the ability of KTR27-F to replicate in and kill normalprimary human fibroblasts is markedly reduced relative to various humantumor cell lines.

Neurovirulence of KTR27-F. The ability of an oncolytic viral recombinantto replicate efficiently in tumor cells must be balanced against thepotentially dangerous side effects of its replication in non-tumortissues. HSV is highly neurotropic, and thus a clinically-relevant HSVrecombinant ideally causes little to no neurovirulence. KTR27 waspreviously demonstrated to be avirulent following intracerebralinoculation in mice (Yao et al., 2010), herein, a similar assay wasconducted with KTR27-F to investigate should the enhanced cytotoxicityof KTR27-F in the presence of tetracycline in cancer cells lead to ahigher degree of neurovirulence. In brief, mice receiving adoxycycline-containing diet or normal diet were intracerebrallyinoculated with KTR27-F at a dose of 1×10⁷ PFU/mouse (FIG. 5), alongwith control groups injected with DMEM or 7134 at a dose of 1×10⁷PFU/mouse, and monitored the mice for 29 days. The groups injected withDMEM, KTR27-F in the presence of doxycycline (T+), and KTR27-F in theabsence of doxycycline (T−) showed no signs of neurovirulence throughoutthe course of the experiment, whereas all of the mice injected with 7134showed signs of central nervous system (CNS) illness commonly associatedwith HSV-1 infection, including roughened fur, hunched posture, ataxia,and anorexia. Six of the eight 7134-inoculated mice died by day 8post-inoculation, and two of the eight fully recovered from CNS illnesswithin 11 days post-inoculation. In light of the demonstration that thedoxycycline concentration in the brains of mice receiving thedoxycycline-containing diet can efficiently release the tetR-mediatedrepression of gene expression following intracerebral inoculation of theT-REx-encoding replication-defective HSV-1 recombinant virus (Yao etal., 2006), the study indicates that the observed avirulence of KTR27-Fin mice receiving a doxycycline-containing diet is primarily the resultof impairment in the ability of KTR27 to replicate in the mouse brain.

Sequence analyses of KTR27-F genome. As expected, sequence analysis ofKTR27-F viral genome confirms that KTR27-F encodes tetR at the HSV-1ICP0 locus, and ICP27 under the control of the tetO-containing ICP27promoter with a self-cleaving ribozyme present at the 5′ untranslatedregion of ICP27 gene. Using the parental wild-type HSV-1 strain KOSgenome as the reference, a total of 58 missense mutations and 2 frameshift mutations are identified in the KTR27-F genome. The UL36 gene ofKTR27-F contains 16 missense mutations and 2 frame shift mutations.Other missense mutations are located in the UL5 gene, the UL8 gene, theUL12 gene, the UL13 gene, the UL16 gene, UL17 gene, UL19 gene, the UL24gene, the UL25 gene, UL26 gene, the UL28 gene, the UL29 gene, the UL30gene, the UL37 gene, the UL39 gene, the UL40 gene, the UL44 gene, UL47gene, the UL52 gene, the UL53 gene (gK), the US1 gene, and the US8 gene.

A single amino acid substitution, Ala to Val at residue 40, isidentified in the gK gene of KTR27-F. The same Ala to Val substitutionhas been identified in the HSV-1 syncytial mutants, syn102, syn105 andsyn 33 (Dolter K E et al., J Virol 68:8277-8281, 1994), which wereisolated from KOS-infected cells in the presence of mutagens,2-aminopurine (Bond V C et al., J Gen Virol 61:245-254, 1982) or5-bromodeoxyuridine (Read G S et al., J Virol 35:105-113, 1980),indicating that the Ala to Val substitution at residue 40 of the gK genein KTR27-F is a key factor for the observed fusogenic phenotype.Syncytial mutations in the gK gene also include Ala to Thr at residue 40in syn20, Asp to Asn at residue 99 in syn31 and syn32, Leu to Pro atresidue 304 in syn30, and Arg to Leu at residue 310 (Dolter K E et al.,J Virol 68:8277-8281, 1994). In addition to the single amino acidsubstitution in the gK gene, KTR27-F contains a single amino acidsubstitution of Ser to Asn in UL24 gene at residue 113. Whether this Serto Asn substitution contributes to the fusogenic activity of KTR27-Fremains to be determined. No mutation is found in the gene encoding gBand the UL20 gene.

Unexpectedly, sequencing analysis of KTR27-F reveals that the HSV-1ICP34.5 gene is missing from the KTR27-F genome. To date, most of HSV-1based oncolytic viruses are based on deletion of the ICP34.5 gene orthrough conditional regulations of ICP34.5 expression (Aghi M andMartuza R L, Oncogen 24:7802-7816, 2005; Lawler S E et al., JAMAOncology, 2016). The ICP35.5 deletion mutant-based HSV-1 oncolyticvirus, T-Vec (Amgen) has been approved for the treatment ofadvanced-stage melanoma in late 2015. Like ICP0, the ICP34.5 gene islocated in the inverted repeat region that flanks the unique long regionof the HSV-1 genome. PCR analyses with primers specific for the ICP34.5gene indicate that while both 7134 and K0R yield a predicatedICP34.5-specific amplified PCR fragment, no ICP34.5-specific DNAfragment was detected in PCR reactions with KTR27, KTR27-F, andK0R27-lacZ viral DNA. PCR analysis with tetR-specific primers confirmthat KTR27, KTR27-F, and K0R27-lacZ encode tetR at the ICP0 locus.Collectively, these results indicate that the ICP34.5 gene was likelylost during the construction of K0R27-lacZ virus.

The various methods and techniques described above provide a number ofways to carry out the application. Of course, it is to be understoodthat not necessarily all objectives or advantages described can beachieved in accordance with any particular embodiment described herein.Thus, for example, those skilled in the art will recognize that themethods can be performed in a manner that achieves or optimizes oneadvantage or group of advantages as taught herein without necessarilyachieving other objectives or advantages as taught or suggested herein.A variety of alternatives are mentioned herein. It is to be understoodthat some preferred embodiments specifically include one, another, orseveral features, while others specifically exclude one, another, orseveral features, while still others mitigate a particular feature byinclusion of one, another, or several advantageous features.

Furthermore, the skilled artisan will recognize the applicability ofvarious features from different embodiments. Similarly, the variouselements, features and steps discussed above, as well as other knownequivalents for each such element, feature or step, can be employed invarious combinations by one of ordinary skill in this art to performmethods in accordance with the principles described herein. Among thevarious elements, features, and steps some will be specifically includedand others specifically excluded in diverse embodiments.

Although the application has been disclosed in the context of certainembodiments and examples, it will be understood by those skilled in theart that the embodiments of the application extend beyond thespecifically disclosed embodiments to other alternative embodimentsand/or uses and modifications and equivalents thereof.

In some embodiments, the terms “a” and “an” and “the” and similarreferences used in the context of describing a particular embodiment ofthe application (especially in the context of certain of the followingclaims) can be construed to cover both the singular and the plural. Therecitation of ranges of values herein is merely intended to serve as ashorthand method of referring individually to each separate valuefalling within the range. Unless otherwise indicated herein, eachindividual value is incorporated into the specification as if it wereindividually recited herein. All methods described herein can beperformed in any suitable order unless otherwise indicated herein orotherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (for example, “such as”) provided withrespect to certain embodiments herein is intended merely to betterilluminate the application and does not pose a limitation on the scopeof the application otherwise claimed. No language in the specificationshould be construed as indicating any non-claimed element essential tothe practice of the application.

Other than in the operating examples, or where otherwise indicated, allnumbers expressing quantities of ingredients or reaction conditions usedherein should be understood as modified in all instances by the term“about.” The term “about” when used in connection with percentages canmean±1%.

Preferred embodiments of this application are described herein,including the best mode known to the inventors for carrying out theapplication. Variations on those preferred embodiments will becomeapparent to those of ordinary skill in the art upon reading theforegoing description. It is contemplated that skilled artisans canemploy such variations as appropriate, and the application can bepracticed otherwise than specifically described herein. Accordingly,many embodiments of this application include all modifications andequivalents of the subject matter recited in the claims appended heretoas permitted by applicable law. Moreover, any combination of theabove-described elements in all possible variations thereof isencompassed by the application unless otherwise indicated herein orotherwise clearly contradicted by context.

All patents, patent applications, publications of patent applications,and other material, such as articles, books, specifications,publications, documents, things, and/or the like, referenced herein arehereby incorporated herein by this reference in their entirety for allpurposes, excepting any prosecution file history associated with same,any of same that is inconsistent with or in conflict with the presentdocument, or any of same that may have a limiting affect as to thebroadest scope of the claims now or later associated with the presentdocument. By way of example, should there be any inconsistency orconflict between the description, definition, and/or the use of a termassociated with any of the incorporated material and that associatedwith the present document, the description, definition, and/or the useof the term in the present document shall prevail.

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Sequence Listing SEQ ID NO: 1 is a nucleotide sequence thatencodes KTR27-F Linear Genome (147,630 bp) (SEQ ID NO: 1)CCCTAGAGGATCTGCGGCTGGAGGGTCGCTGACGGAGGGTCCCTGGGGGTCGCAACGTAGGCTTTTCTTCTTTTTTTCTTCTTCCCTCCCCCGCCCGAGGGGGCGCCCGAGTCTGCCTGGCTGCTGCGTCTCGCTCCGAGTGCCGAGGTGCAAATGCGACCAGACCGTCGGGCCAGGGCTAACTTATACCCCACGCCTTTCCCCTCCCCAAAGGGGCGGCAGTGACGATTCCCCCAATGGCCGCGCGTCCCAGGGGAGGCAGGCCCACCGCGGAGCGGCCCCGTCCCCGGGGACCAACCCGGCGCCCCCAAAGAATATCATTAGCATGCACGGCCCGGCCCCCGATTTGGGGGACCAACCCGGTGTCCCCCAAAGAACCCCATTAGCATGCCCCTCCCGCCGACGCAACAGGGGCTTGGCCTGCGTCGGTGCCCCGGGGCTTCCCGCCTTCCCGAAGAAACTCATTACCATACCCGGAACCCCAGGGGACCAATGCGGGTTCATTGAGCGACCCGCGGGCCACTGCGCGAGGGGCCGTGTGTTCCGCCAAAAAAGCAATTAACATAACCCGGAACCCCAGGGGAGTGGTTACGCGCGGCGCGGGAGGCGGGGAATACCGGGGTTGCCCATTAAGGGCCGCGGGAATTGCCGGAAGCGGGAAGGGCGGCCGGGGCCGCCCATTAATGAGTTTCTAATTACCATCCCGGGAAGCGGAACAAGGCCTCTGCAAGTTTTTAATTACCATACCGGGAAGTGGGCGGCCCGGCCCACTGGGCGGGAGTTACCGCCCAGTGGGCCGGGCCCCGACGACTCGGCGGACGCTGGTTGGCCGGGCCCCGCCGCGCTGGCGGCCGCCGATTGGCCAGTCCCGCCCCCCGAGGGCGGGCCCGCCTCGGGGGCGGGCCGGCCCCAAGCGAATATGCGCGGCTCCTGCCTTCGTCTCTCCGGAGAGCGGCTTGGTGGCGGGGCCCGGCCACCAGCGTCCGCCGAGTCGTCGGGGCCCGGCCCACTGGGCGGTAACTCCCGCCCAGTGGGCCGGGCCGCCCACTTCCCGGTATGGTAATTAAAAACTTGCAGAGGCCTTGTTCCGCTTCCCGGTATGGTAATTAGAAACTCATTAATGGGCGGCCCCGGCCGCCCTTCCCGCTTCCGGCAATTCCCGCGGCCCTTAATGGGCAACCCCGGTATTCCCCGCCTCCCGCGCCGCGCGTAACCACTCCCCTGGGGTTCCGGGTTATGTTAATTGCTTTTTTGGCGGAACACACGGCCCCTCGCGCATTGGCCCGCGGGTCGCTCAATGAACCCGCATTGGTCCCCTGGGGTTCCGGGTATGGTAATGAGTTTCTTCGGGAAGGCGGGAAGCCCCGGGGCACCGACGCAGGCCAAGCCCCTGTTGCGTCGGCGGGAGGGGCATGCTAATGGGGTTCTTTGGGGGACACCGGGTTGGTCCCCCAAATCGGGGGCCGGGCCGTGCATGCTAATGATATTCTTTGGGGGCGCCGGGTTGGTCCCCGGGGACGGGGCCGCTCCGCGGTGGGCCTGCCTCCCCTGGGACGCGCGGCCATTGGGGGAATCGTCACTGCCGCCCCTTTGGGGAGGGGAAAGGCGTGGGGTATAAGTTAGCCCTGGCCCGACGGTCTGGTCGCATTTGCACCTCGGCACTCGGAGCGAGACGCAGCAGCCAGGCAGACTCGGGCCGCCCCCTCTCCGCATCACCACAGAAGCCCCGCCTACGTTGCGACCCCCAGGGACCCTCCGTCAGCGACCCTCCAGCCGCATACGACCCCCCGGGGATCCTCTAGGGCCTCTGAGCTATTCCAGAAGTAGTGAAGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTCCGGATCGATCCTGAGAACTTCAGGGTGAGTTTGGGGACCCTTGATTGTTCTTTCTTTTTCGCTATTGTAAAATTCATGTTATATGGAGGGGGCAAAGTTTTCAGGGTGTTGTTTAGAATGGGAAGATGTCCCTTGTATCACCATGGACCCTCATGATAATTTTGTTTCTTTCACTTTCTACTCTGTTGACAACCATTGTCTCCTCTTATTTTCTTTTCATTTTCTGTAACTTTTTCGTTAAACTTTAGCTTGCATTTGTAACGAATTTTTAAATTCACTTTTGTTTATTTGTCAGATTGTAAGTACTTTCTCTAATCACTTTTTTTTCAAGGCAATCAGGGTATATTATATTGTACTTCAGCACAGTTTTAGAGAACAATTGTTATAATTAAATGATAAGGTAGAATATTTCTGCATATAAATTCTGGCTGGCGTGGAAATATTCTTATTGGTAGAAACAACTACATCCTGGTCATCATCCTGCCTTTCTCTTTATGGTTACAACGATATACACTGTTTGAGATGAGGATAAAATACTCTGAGTCCAAACCGGGCCCCTCTGCTAACCATGTTCATGCCTTCTTCTTTTTCCTACAGCTCCTGGGCAACGTGCTGGTTATTGTGCTGTCTCATCATTTTGGCAAAGAATTGTAATACGACTCACTATAGGGCGAATTGATATGTCTAGATTAGATAAAAGTAAAGTGATTAACAGCGCATTAGAGCTGCTTAATGAGGTCGGAATCGAAGGTTTAACAACCCGTAAACTCGCCCAGAAGCTAGGTGTAGAGCAGCCTACATTGTATTGGCATGTAAAAAATAAGCGGGCTTTGCTCGACGCCTTAGCCATTGAGATGTTAGATAGGCACCATACTCACTTTTGCCCTTTAGAAGGGGAAAGCTGGCAAGATTTTTTACGTAATAACGCTAAAAGTTTTAGATGTGCTTTACTAAGTCATCGCGATGGAGCAAAAGTACATTTAGGTACACGGCCTACAGAAAAACAGTATGAAACTCTCGAAAATCAATTAGCCTTTTTATGCCAACAAGGTTTTTCACTAGAGAATGCATTATATGCACTCAGCGCTGTGGGGCATTTTACTTTAGGTTGCGTATTGGAAGATCAAGAGCATCAAGTCGCTAAAGAAGAAAGGGAAACACCTACTACTGATAGTATGCCGCCATTATTACGACAAGCTATCGAATTATTTGATCACCAAGGTGCAGAGCCAGCCTTCTTATTCGGCCTTGAATTGATCATATGCGGATTAGAAAAACAACTTAAATGTGAAAGTGGGTCCGCGTACAGCGGATCCCGGGAATTCAGATCTTATTAAAGCAGAACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACAAATAAAGCATTTTTTTCACTGCATTCTAGTTGTGGTTTGTCCAAACTCATCAATGTATCTTATCATGTCTGGTCGACCCGGGACGAGGGAAAACAATAAGGGACGCCCCCGTGTTTGTGGGGAGGGGGGGGTCGGGCGCTGGGTGGTCTCTGGCCGCGCCCACTACACCAGCCAATCCGTGTCGGGGAGGTGGAAAGTGAAAGACACGGGCACCACACACCAGCGGGTCTTTTGTGTTGGCCCTAATAAAAAAAACTCAGGGGATTTTTGCTGTCTGTTGGGAAATAAAGGTTTACTTTTGTATCTTTTCCCTGTCTGTGTTGGATGTATCGCGGGGGTGCGTGGGAGTGGGGGCCCCCACTCCCACGCACCCCCACTCCCACGCACCCCCACTCCCACGCACCCCCGCGATACATCCAACACAGACAGGGAAAAGATACAAAAGTAAACCTTTATTTCCCAACAGACAGCAAAAATCCCCTGAGTTTTTTTTATTAGGGCCAACACAAAAGACCCGCTGGTGTGTGGTGCCCGTGTCTTTCACTTTCCACCTCCCCGACACGGATTGGCTGGTGTAGTGGGCGCGGCCAGAGACCACCCAGCGCCCGCCCCCCCCCCCCCCACAACCCCGGGGGCGTCCCTTATTGTTTCCCTCGTCCCGGGTCGACGTCGACCCGGGACGAGGGAAAACAATAAGGGACGCCCCCGTGTTTGTGGGGAGGGGGGGGTCGGGCGCTGGGTGGTCTCTGGCCGCGCCCACTACACCAGCCAATCCGTGTCGGGGAGGTGGAAAGTGAAAGACACGGGCACCACACACCAGCGGGTCTTTTGTGTTGGCCCTAATAAAAAAAACTCAGGGGATTTTTGCTGTCTGTTGGGAAATAAAGGTTTACTTTTGTATCTTTTCCCTGTCTGTGTTGGATGTATCGCGGGGGTGCGTGGGAGTGGGGGTGCGTGGGAGTGGGGGTGCGTGGGAGTGGGGGTGGGGGGGGGGGTGCGTGGGGGAGGGGGGGCGTGGGAGTGGGGGTGCGTGGGGGTGGGGGTGCGTGGGAGTGGCCCGGAGAGCCGCGGCCCCCGGACGCGCCCGGAAAGTCTTTCGCCCACCGGCGATCGGCACGGCCGCACCCCCGCTTTTATAAAGGCTCAGATGACGCAGCAAAAACAGGCCACAGCACCACATGGGTAGGGGATGTAATTTTATTTTCCTCGTCTGCGGCCTAATGGATTTCCGGGCGCGGTGCCCCTGTCTGCAGAGCACTTAACGGATTGATATCTCGCGGGCACGCGCGCCCTTAAGGGGCCGGGGGGGGCGGGGGGCCGGATACCCACACGGGCGGGGGGGGGTGTCGCGGGCCGTCTGCTGGCCCGCGGCCACATAAACAATGACTCGGGGCCTTTCTGCCTCTGCCGCTTGTGTGTGCGCGCGCCGGCTCTGCGGTGTCGGCGGCGGCGGCGGCGGTGGCCGCCGTGTTCGGTCTCGGTAGCCGGCCGGCGGGGGACTCGCGGGGGGCCGGAGGGTGGAAGGCAGGGGGGTGTAGGATGGGTATCAGGACTTCCACTTCCCGTCCTTCCATCCCCCGTTCCCCTCGGTTGTTCCTCGCCTCCCCCAACACCCCGCCGCTTTCCGTTGGGGTTGTTATTGTTGTCGGGATCGTGCGGGCCGGGGGTCGCCGGGGCAGGGGCGGGGGCGTGGGCGGGGGTGCTCGTCGATCGACCGGGCTCAGTGGGGGCGTGGGGTGGGTGGGAGAAGGCGAGGAGACTGGGGTGGGGGCGCCCCCACTGAGCCCGGTCGATCGACGAGCACCCCCGCCCCCCCCCGCCCCTGCCCCGGCGACCCCCGGCCCGCACGATCCCGACAACAATAACAACCCCAACGGAAAGCGGCGGGGTGTTGGGGGAGGCGAGGAACAACCGAGGGGAACGGGGGATGGAAGGACGGGAAGTGGAAGTCCTGATACCCATCCTACCCCCCCCTGCCTTCCCCCCTCCGGCCCCCCGCGAGTCCACCCGCCGGCCGGCTACCGAGACCGAACACGGCGGCCACCGCCGCCGCCGCCGCCGACACCGCAGAGCCGGCGCGCGCACACACAAGCGGCAGAGGCAGAAAGGCCCCGAGTCATTGTTTATGTGGCCGCGGGCCAGCAGACGGCCCGCGACACCCCCCCCCGCCCGTGTGGGTATCCGGCCCCCCGCCCCGCGCCGGCCCCTTAAGGGCGCGCGTGCCCGCGAGATATCAATCCGTTAAGTGCTCTGCAGACAGGGGCACCGCGCCCGGAAATCCATTAGGCCGCAGACGAGGAAAATAAAATTACATCACCTACCCATGTGGGCTGTGGCCTGTTTTGCTGCGTCATCTGAGCCTTTATAAAAGCGGGGGCGCGGTCGTTCCGATCGCCGGTGGTGCGAAAGACTTTCCGGGCGCTGGGGTGGGGGTGTCGGTGGGTGGTTGTTTTTTTTTTTGTGGTTGTTTTTTGTGTCTGTTTCCGTCCCCCGTCACCCCCCTCCCTCCGTCCCCTCCGTCCCCCCGTCGCGGGTGTTTGTGTTTGTTTATTCCGACATCGGTTTATTTAAAATAAACACAGCCGTTCTGCGTGTCTGTTCTTGCGTGTGGCTGGGGGCTTATATGTGGGGTCCCGGGGGCGGGATGGGGTTTAGCGGCGGGGGGCGGCGCGCCGGACGGGGCGCTGGAGATAACGGCCCCCGGGGAACGGGGGACCGGGGCTGGGTATCCCGAGGTGGGTGGGTGGGCGGCGGTGGCCGGGCCGGGCCGGGCCGGGCCGGGCCAGCGCCCCGCCGGCCCCCCCCCCCGCCGCTAAACCCCATCCCGCCCCCGGGACCCCACATATAAGCCCCCAGCCACACGCAAGAACAGACACGCAGAACGGCTGTGTTTATTTTAAATAAACCGATGTCGGAATAAACAAACACAAACACCCGCGACGGGGGGACGGAGGGGACGGAGGGAGGGGGGTGACGGGGGACGGAAACAGACACAAAAAACAACCACAAAAAAAAAAACAACCACCCACCGCACCCCCCCCCTTCTCCTCCTCCTCCTCGTTTTCCAACCCCGCCCACCCGGCCCGGCCCGGCCCGGCCCGGCCCCGCCGCCCACCCACCCACCTCGGGATACCCAGCCCCGGTCCCCCGTTCCCCGGGGGCCGTTATCTCCAGCGGGGGTTTGGAAAAACGAGGAGGAGGAGGAGAAGGCGGGGGGGGAGACGGGGGGAAAGCAAGGACACGGCCCGGGGGGTGGGAGCGCGGGCCGGGCCGCTCGTAAGAGCCGCGACCCGGCCGCCGGGGAGCGTTGTCGCCGTCGGTCTGCCGGCCCCCGTCCCTCCCTTTTTTGACCAACCAGCGCCCTCCCCCCCACCACCATTCCTACTACCACCACCACCACCACCCCCACCACCGACACCTCCCGCGCACCCCCGCCCACATCCCCCCACCCCGCACCACGAGCACGGGGTGGGGGTAGCAGGGGATCAAAGGGGGGCAAAGCCGGCGGGGCGGTTCGGGGGGGCGGGAGACCGAGTAGGCCCGCCCATACGCGGCCCCTCCCGGCAGCCACGCCCCCCAGCGTCGGGTGTCACGGGGAAAGAGCAGGGGAGAGGGGAGAGGGGGGGAGAGGGGGTATATAAACCAACGAAAAGCGCGGGAACGGGGATACGGGGCTTGTGTGGCACGACGTCGTGGTTGTGTTACTGGGCAAACACTTGGGGACTGTAGGTTTCTGTGGGTGCCGACCCTAGGCGCTATGGGGATTTTGGGTTGGGTCGGGCTTATTGCGGTTGGGGTTTTGTGTGTGCGGGGGGGCTTGTCTTCAACCGAATATGTTATTCGGAGTCGGGTGGCTCGAGAGGTGGGGGATATATTAAAGGTGCCTTGTGTGCCGCTCCCGTCTGACGATCTTGATTGGCGTTACGAGACCCCCTCGGCTATAAACTATGCTTTGATAGACGGTATATTTTTGCGTTATCACTGTCCCGGATTGGACACGGTCTTGTGGGATAGGCATGCCCAGAAGGCATATTGGGTTAACCCCTTTTTATTTGTGGCGGGTTTTCTGGAGGACTTGAGTCACCCCGCGTTTCCTGCCAACACCCAGGAAACAGAAACGCGCTTGGCCCTTTATAAAGAGATACGCCAGGCGCTGGACAGTCGCAAGCAGGCCGCCAGCCACACACCTGTGAAGGCTGGGTGTGTGAACTTTGACTATTCGCGCACCCGCCGCTGTGTAGGGCGACAGGATTTGGGACCTACCAACGGAACGTCTGGACGGACCCCGGTTCTGCCGCCGGACGATGAAGCGGGCCTGCAACCGAAGCCCCTCACCACGCCGCCGCCCATCATCGCCACGTCGGCCCCCACCCCGCGACGGGACGCCGCCACAAAAAGCAGACGCCGACGACCCCACTCCCGGCGCCTCTAACGATGCCTCGACGGAAACCCGTCCGGGTTCGGGGGGCGAACCGGCCGCCTGTCGCTCGTCAGGGCCGGCGGGCGCTCCTCGCCGCCCTAGAGGCTGTCCCGCTGGTGTGACGTTTTCCTCGTCCGCGCCCCCCGACCCTCCCATGGATTTAACAAACGGGGGGGTGTCGCCTGCGGCGACCTCGGCGCCTCTGGACTGGACCACGTTTCGGCGTGTGTTTCTGATCGACGACGCGTGGCGGCCCCTGATGGAGCCTGAGCTGGCGAACCCCTTAACCGCCCACCTCCTGGCCGAATATAATCGTCGGTGCCAGACCGAAGAGGTGCTGCCGCCGCGGGAGGATGTGTTTTCGTGGACTCGTTATTGCACCCCCGACGAGGTGCGCGTGGTTATCATCGGCCAGGACCCATATCACCACCCCGGCCAGGCGCACGGACTTGCGTTTAGCGTGCGCGCGAACGTGCCGCCTCCCCCGAGTCTTCGGAATGTCTTGGTGGCCGTCAAGAACTGTTATCCCGAGGCACGGATGAGCGGCCACGGTTGCCTGGAAAAGTGGGCGCGGGACGGCGTCCTGTTACTAAACACGACCCTGACCGTCAAGCGCGGGGCGGCGGCGTCCCACTCTAGAATCGGTTGGGACCGCTTCGTGGGCGGAGTTATCCGCCGGTTGGCCGCGCGCCGCCCCGGCCTGGTGTTTATGCTCTGGGGCGCACACGCCCAGAATGCCATCAGGCCGGACCCTCGGGTCCATTGCGTCCTCAAGTTTTCGCACCCGTCGCCCCTCTCCAAGGTTCCGTTCGGAACCTGCCAGCATTTCCTCGTGGCGAACCGATACCTCGAGACCCGGTCGATTTCACCCATCGACTGGTCGGTTTGAAAGGCATCGACGTCCGGGGTTTTTGTCGGTGGGGGCTTTTGGGTATTTCCGATGAATAAAGACGGTTAATGGTTAAACCTCTGGTCTCATACGGGTCGGTGATGTCGGGCGTCGGGGGAGAGGGAGTTCCCTCTGCGCTTGCGATTCTAGCCTCGTGGGGCTGGACGTTCGACACGCCAAACCACGAGTCGGGGATATCGCCAGATACGACTCCCGCAGATTCCATTCGGGGGGCCGCTGTGGCCTCACCTAACCAACCTTTACCGGGGGCCCGGAACGGGAGGCCCAGCGCCGTCTTTCTCCCCAACGCGCGCGGATGACGGCCCGCCCTGTACCGACGGGCCCTACGTGACGTTTGATACCCTGTTTATGGTGTCGTCGATCGACGAATTAGGGCGTCGCCAGCTCACGGACACCATCCGCAAGGACCTGCGGTTGTCGCTGGCCAAGTTTAGCATTGCGTGCACCAAGACCTCCTCGTTTTCGGGAAACGCCCCGCGCCACCACAGACGCGGGGCGTTCCAGCGCGGCACGCGGGCGCCGCGCAGCAACAAAAGCCTCCAGATGTTTGTGTTGTGCAAACGCGCCCACGCCGCTCGAGTGCGAGAGCAGCTTCGGGTCGTTATTCAGTCCCGCAAGCCGCGCAAGTATTACACGCGATCTTCGGACGGGCGGCTCTGCCCCGCCGTCCCCGTGTTCGTCCACGAGTTCGTCTCGTCCGAGCCAATGCGCCTCCACCGAGATAACGTCATGCTGGCCTCGGGGGCCGAGTAACCGCCCCCCCCCCATGCCACCCTCACTGCCCGTCGCGCGTGTTTGATGTTAATAAATAACACATAAATTTGGCTGGTTGTTTGTTGTCTTTAATGGACCGCCCGCAAGGGGGGGGGGGCGTTTCAGTGTCGGGTGACGAGCGCGATCCGGCCGGGATCCTAGGACCCCAAAAGTTTGTCTGCGTATTCCAGGGTGGGGCTCAGTTGAATCTCCCGCAGCACCTCTACCAGCAGGTCCGCGGTGGGCTGGAGAAACTCGGCCGTCCCGGGGCAGGCGGTTGTCGGGGGTGGAGGCGCGGCGCCCACCCCGTGTGCCGCGCCTGGCGTCTCCTCTGGGGGCGACCCGTAAATGGTTGCAGTGATGTAAATGGGTCCGCGGTCCAGACCACGGTCAAAATGCCGGCCGTGGCGCTCCGGGCGCTTTCGCCGCGCGAGGAGCTGACCCAGGAGTCGAACGGATACGCGTACATATGGGCGTCCCACCCGCGTTCGAGCTTCTGGTTGCTGTCCCGGCCTATAAAGCGGTAGGCACAAAATTCGGCGCGACAGTCGATAATCACCAACAGCCCAATGGGGGTGTGCTGGATAACAACGCCTCCGCGCGGCAGGCGGTCCTGGCGCTCCCGGCCCCGTACCATGATCGCGCGGGTGCCGTACTCAAAAACATGCACCACCTGCGCGGCGTCGGGCAGTGCGCTGGTCAGCGAGGCCCTGGCGTGGCATAGGCTATACGCGATGGTCGTCTGTGGATTGGACATCTCGCGGTGGGTAGTGAGTCCCCCGGGCCGGGTTCGGTGGAACTGTAAGGGGACGGCGGGTTAATAGACAATGACCACGTTCGGATCGCGCAGAGCCGATAGTATGTGCTCACTAATGACGTCATCGCGCTCGTGGCGCTCCCGGAGCGGATTTAAGTTCATGCGAAGGAATTCGGAGGAGGTGGTGCGGGACATGGCCACGTACGCGCTGTTGAGGCGCAGGTTGCCGGGCGTAAAGCAGATGGCGACCTTGTCCAGGCTAAGGCCCTGGGAGCGCGTGATGGTCATGGCAAGCTTGGAGCTGATGCCGTAGTCGGCGTTTATGGCCATGGCCAGCTCCGTAGAGTCAATGGACTCGACAAACTCGCTGATGTTGGTGTTGACGACGGACATGAAGCCGTGTTGGTCACGCAAGACCACGTAAGGCAGGGGGGCCTCTTCCAGTAACTCGGCCACGTTGGCCGTCGCGTGCCGCCTCCGCAGCTCGTCCGCAAAGGCAAACACCCGTGTGTACGTGTATCCCATGAGCGTATAATTGTCCGTCTGCAGGGCGACGGACATCAGCCCCCCGCGCGGCGAGCCGGTCAGCATCTCGCAGCCCCGGAAGATAACGTTGTCCACGTACGTGCTAAAGGGGGCGACTTCAAATGCCTCCCCGAAGAGCTCTTGGAGGATTCGGAATCTCCCGAGGAAGGCCCGCTTCAGCAGCGCAAACTGGGTGTGAACGGCGGCGGTGGTCTCCGGTTCCCCGGGGGTGTAGTGGCAGTAAAACACGTCGAGCTGTTGTTCGTCCAGCCCCGCGAAAATAACGTCGAGGTCGTCGTCGGGAAAATCGTCCGGGCCCCCGTCCCGCGGCCCCAGTTGCTTAAAATCAAACGCACGCTCGCCGGGGGCGCCTGCGTCGGCCATTACCGACGCCTGCGTCGGCACCCCCGAAGATTTGGGGCGCAGAGACAGAATCTCCGCCGTTAGTTCTCCCATGCGGGCGTACGCGAGGGTCCTCTGGGTCGCATCCAGGCCCGGGCGCTGCAGAAAGTTGTAAAAGGAGATAAGCCCGCTAAATATGAGCCGCGACAGGAACCTGTAGGCAAACTCCACCGAAGTCTCCCCCTGAGTCTTTACAAAGCTGTCGTCACGCAACACTGCCTCGAAGGCCCGGAACGTCCCACTAAACCCAAAAACCAGTTTTCGCAGGCGCGCGGTCACCGCGATCTGGCTGTTGAGGACGTAAGTGACGTCGTTGCGGGCCACGACCAGCTGCTGTTTGCTGTGCACCTCGCAGCGCATGTGCCCCGCGTCCTGGTCCTGGCTCTGCGAGTAGTTGGTGATGCGGCTGGTGTTGGCCGTGAGCCACTTTTCAATAGTCAGGCCGGGCTGGTGTGTCAGCCGTCGGTAGTGTTCAAACTCCTTGACCGACACGAACGTAAGCACGGGGAGGTGTAGCCGTCGGTATTCGTCAAACTCCTTTCCCTCCCCTCCCTTCCTCCCTTTTCTTTTTCCCACTCCGCCCTCCCCCTCACGGGTCACCTTCAGGTAGGCGTGGAGCTTGGCCATGTACGCGCTCACCTCTTTGTGGGAGGAGAACAGCCGCGTCCAGCCGGGGAGGTTGGCGGGGTTGGTGATGTAGTTTTCCGGGACGACGAAGCGATCCACGAACTGCATGTGCTCCTCGGTGATGGGCAGGCCGTACTCCAGCACCTTCATGAGGTTACCGAACTCGTGCTCGACGCACCGTTTGTTGTTAATAAAAATGGCCCAGCTATACGAGAGGCGGGCGTACTCGCGCAGCGTGCGGTTGCAGATGAGGTACGTGAGCACGTTCTCGCTCTGGCGGACGGAACACCGCAGTTTCTGGTGCTCGAAGGTCGACTCCAGGGACGCCGTCTGCGTCGGCGAGCCCCCACACACCAACACGGGCCGCAGGCGGGCCGCGTACTGGGGGGTGTGGTACAGGGCGTTAATCATCCACCAGCAATACACCACGGCCGTGAGGAGGTGACGCCCAAGGAGCCCGGCCTCGTCGATGACGATCACGTTGCTGCGGGTAAAGGCCGGCAGCGCCCCGTGGGTGGCCGGGGCCAACCGCGTCAGGGCGCCCTCGGCCAACCCCAGGGTCCGTTCCAGGGCGGCCAGGGCGCGAAACTCGTTCCGCAACTCCTCGCCCCCGGAGGCGGCCAGGGCGCGCTTCGTGAGGTCCAAAATCACCTCCCAGTAGTACGTCAGATCTCGTCGCTGCAGGTCCTCCAGCGAGGCGGGGTTGCTGGTCAGGGGGTACGGGTACTGTCCCAGTTGGGCCTGGACGTGATTCCCGCGAAACCCAAATTCATGAAAGATGGTGTTGATGGGTCGGCTGAGAAAGGCGCCCGAGAGTTTGGCGTACATGTTTTGGGCCGCAATGCGCGTGGCGCCCGTCACCACACAGTCCAAGACCTCGTTGATTGTCTGCACGCACGTGCTCTTTCCGGAGCCAGCGTTGCCGGTGATAAGATACACCGCGAACGGAAACTCCCTGAGGGGCAGGCCTGCGGGGGACTCTAAGGCCGCCACGTCCCGGAACCACTGCAGACGGGGCACTTGCGCTCCGTCGAGCTGTTGTTGCGAGAGCTCTCGGATGCGCTTAAGGATTGGCTGCACCCCGTGCATAGACGTAAAATTTAAAAAGGCCTCGGCCCTCCCTGGAACGGCTGGTCGGTCCCCGGGTTGCTGAAGGTGCGGCGGGCCGGGTTTCTGTCCGTCTAGCTGGCGCTCCCCGCCGGCCGCCGCCATGACCGCACCACGCTCGTGGGCCCCCACTACGCGTGCGCGGGGGGACACGGAAGCGCTGTGCTCCCCCGAGGACGGCTGGGTAAAGGTTCACCCCACCCCCGGTACGATGCTGTTCCGTGAGATTCTCCACGGGCAGCTGGGGTATACCGAGGGCCAGGGGGGGTACAACGTCGTCCGGTCCAGCGAGGCGACCACCCGGCAGCTGCAGGCGGCGATCTTTCACGCGCTCCTCAACGCCACCACTTACCGGGACCTCGAGGCGGACTGGCTCGGCCACGTGGCGGCCCGCGGTCTGCAGCCCCAACGGCTGGTTCGCCGGTACAGGAACGCCCGGGAGGCGGATATCGCCGGGGTGGCCGAGCGGGTGTTCGACACGTGGCGGAACACGCTTAGGACGACGCTGCTGGACTTTGCCCACGGGTTGGTCGCCTGCTTTGCGCCGGGCGGCCCGAGCGGCCCGTCAAGCTTCCCCAAATATATCGACTGGCTGACGTGCCTGGGGCTGGTCCCCATATTACGCAAGCGACAAGAAGGGGGTGTGACGCAGGGTCTGAGGGCGTTTCTCAAGCAGCACCCGCTGACCCGCCAGCTGGCCACGGTCGCGGAGGCCGCGGAGCGCGCCGGCCCCGGGTTTTTTGAGCTGGCGCTGGCCTTCGACTCCACGCGCGTGGCGGACTACGACCGCGTGTATATCTACTACAACCACCGCCGGGGCGACTGGCTCGTGCGAGACCCCATCAGCGGGCAGCGCGGAGAATGTCTGGTGCTGTGGCCCCCCTTGTGGACCGGGGACCGTCTGGTCTTCGATTCGCCCGTCCAGCGGCTGTTTCCCGAGATCGTCGCGTGTCACTCCCTCCGGGGACACGCGCACGTCTGCCGGCTGCGCAATACCGCGTCCGTCAAGGTGCTGCTGGGGCGCAAGAGCGACAGCGAGCGCGGGGTGGCCGGTGCCGCGCGGGTCGTTAACAAGGTGTTGGGGGAGGACGACGAGACCAAGGCCGGGTCGGCCGCCTCGCGCCTCGTGCGGCTTATCATCAACATGAAGGGCATGCGCCACGTAGGCGACATTAACGACACCGTGCGTGCCTACCTCGACGAGGCCGGGGGGCACCTGATAGACGCCCCGGCCGTCGACGGTACCCTCCCTGGATTCGGCAAGGGCGGAAACAACCGCGGGTCTGCGGGCCAGGACCAGGGGGGGCGGGCGCCGCAGCTTCGCCAGGCCTTCCGCACGGCCGTGGTTAACAACATCAACGGCGTGTTGGAGGGCTATATAAATAACCTGTTTGGAACCATCGAGCGCCTGCGCGAGACCAACGCGGGCCTGGCGACCCAATTGCAGGAGCGCGACCGCGAGCTCCGGCGCGCAACAGCGGGGGCCCTGGAGCGCCAGCAGCGCGCGGCCGACCTGGCGGCCGAGTCCGTGACCGGTGGATGCGGCAGCCGCCCTGCGGGGGCGGACCTGCTCCGGGCCGACTATGACATTATCGACGTCAGCAAGTCCATGGACGACGACACGTACGTCGCCAACAGCTTTCAGCACCCGTACATCCCTTCGTACGCCCAGGACCTGGAGCGCCTGTCGCGCCTCTGGGAGCACGAGCTGGTGCGCTGTTTTAAAATTCTGTGTCACCGCAACAACCAGGGCCAAGAGACGTCGATCTCGTACTCCAGCGGGGCGATCGCCGCATTCGTCGCCCCCTACTTTGAGTCAGTGCTTCGGGCCCCCCGGGTAGGCGCGCCCATCACGGGCTCCGATGTCATCCTGGGGGAGGAGGAGTTATGGGATGCGGTGTTTAAGAAAACCCGCCTGCAAACGTACCTGACAGACATCGCGGCCCTGTTCGTCGCGGACGTCCAGCACGCAGCGCTGCCCCCGCCCCCCTCCCCGGTCGGCGCCGATTTCCGGCCCGGCGCGTCCCCGCGGGGCCGGTCCAGACGCGGTCGCCCGGAAGGAAGAACGGCGCCAGGCGCGCCGGACCAGGGCGGGGGCATCGGGCACCGGGATGGCCGCCGCGACGGCCGACGATGAGGGGTCGGCCGCCACCATCCTCAAGCAGGCCATCGCCGGGGACCGCAGCCTGGTCGAGGCGGCCGAGGCGATTAGCCAGCAGACGCTGCTCCGCCTGGCCTGCGGGTGCGCCAGGTCGGCGCCGCCAGCCGCGGTTTACCGCCACCAGCATCGCGCGCGTCGACGTCGCGCCTGGGTGCCGGTTGCGGTTCGTTCTGGACGGGAGTCCCGAGGACGCCTATGTGACGTCGGAGGATTACTTTAAGCGCTGCTGCGGCCAGTCCAGTTATCGCGGCTTCGCGGTGGCGGTCCTGACGGCCAACGAGGACCACGTGCACAGCCTGGCCGTGCCCCCCCTCGTTCTGCTGCACCGGTTCTCCCTGTTCAACCCCAGGGACCTCCTGGACTTTGAGCTTGCCTGTCTGCTGATGTACCTGGAGAACTGCCCCCGAAGCCACGCCACCCCGTCGACCTTTGCCAAGGTTCTGGCGTGGCTCGGGGTCGCGGGTCGCCGCACGTCCCCATTCGAACGCGTTCGCTGCCTTTTCCTCCGCAGTTGCCACTGGGTCCTAAACACACTCATGTTCATGGTGCACGTAAAACCGTTCGACGACGAGTTCGTCCTGCCCCACTGGTACATGGCCCGGTACCTGCTGGCCAACAACCCGCCCCCCGTTCTCTCGGCCCTGTTCTGTGCCACCCCGACGAGCTCCTCATTCCGGCTGCCGGGGCCGCCCCCCCGCTCCGACTGCGTGGCCTATAACCCCGCCGGGATCATGGGGAGCTGCTGGGCGTCGGAGGAGGTGCGCGCGCCTCTGGTCTATTGGTGGCTTTCGGAGACCCCAAAACGACAGACGTCGTCGCTGTTTTATCAGTTTTGTTGAATTTTAGGAAATAAACCCGGTTTTGTTTCTGTGGCCTCCCGACGGATGCGCGTGTCCTTCCTCCGTCTTGGTGGGTGGGTGTCTGTGTATCCGTCCCATCTGTGCGGAGAGGGGGGGCATGTCGGCACGTATTCGGACAGACTCAAGCACACACGGGGGAGCGCTCTTGTCTCAGGGCAATGTTTTTATTGGTCAAACTCAGGCAAACAGAAACGACATCTTGTCGTCAAAGGGATACACAAACTTCCCCCCCTCTCCCCATACTCCCGCCAGCACCCCGGTAAACACCAACTCAATCTCGCGCAGGATTTCGCGCAGGTGATGAGCGCAGTCCACGGGGGGGAGCACAAGGGGCCGCGGGTGTAGATCGAGGGGACGCCGACCGACTCACCGCCTCCGGGACAGACACGCACGACGCGCCGCCAGTAGTGCTCTGCGTCCAGCAAGGCGCCGCCGCGGAAGGCAGTGGGGGGCAAGGGGTCGCTAGCCTCAAGGGGGACACCCGAACGCTCCAGTACTCCGCGTCCAACCGTTTATTAAACGCGTCCACGATAAGGCGGTCGCAGGCGTCCTCCATAAGGCCCCGGGCCGTGAGTGCGTCCTCCTCCGGCACGCCTGCCGTTGTCAGGCCCAGGACCCGTCGCAGCGTGTCGCGTACGACCCCGGCCGCCGTGGTGTACGCGGGCCCGCGGAGAGGAAATCCCCCAAGATGGTCAGTGTTGTCGCGGGAGTTCCAGAACCACACTCCCGCCTGGTTCCAGGCGACTGCGTGGGTGTAGACGCCCTCGAGGGCCAGGCACAGTGGGTGCCGCAGCCGGAGGCCGTTGGCCCTAAGCACGCTCCACGGCCGTCTCGATGGCCCGCCGGGCGTCCTCGATCCCCCGGAAGCCGCATCCGCGTCTTGGGGGTCCACGTTAAAGACACCCCAGAACGCACCCCCATCGCCCCCGCAGACCGCGAACTTCACCGAGCTGGCCGTCTCCTCGATCTGCAGGCAGACGGCGGCCATTACCCCACCCAGGAGCTGCCGCAGCGCAGGGCAGGCGTCGCACGTGTCCGGGACCAGGCGCTCCAAGACGGCCCCGGCCCAGGGCTCTGAGGGAGCGGCCACCACCAGCGCGTCCAGTCTTGCTAGGCCCGTCCGGCCGTGGGGGTCCGCCAGCCCGCTCCCCCCGAGGTCGGCAAGGACAAAAGGAGCTGGGCGCGAAGTCCGGGGAAGCAAAACCGCGCCGTCCAGACGGGCCCGACGGCCGCGGGCGGGTCTAACAGTTGGATGATTTTAGTGGCGGGATGCCACCGCGCCACCGCCTCCCGCACCGCGGGCAGGAGGCATCCGGCTGCCGCCGAGGCCACGCCGGGCCAGGCTCGCGGGGGGAGGACGACCCTGGCCCCCACCGCGGGCCAGGCCCCCAGGAGCGCGGCGTAAGCGGCCGCGGCCCCGCGCACCAGGTCCCGTGCCGACTCGGCCGTGGCCGGCACGGTGAACGTGGGCCAACCCGGAAACCCCAGGACGGCAAAGTACGGGACGGGTCCCCCCCGGACCTCAAACTCGGGCCCCAGAAAGGCAAAGACGGGGGCCAGGGCCCCGGGGGCGGCGTGGACCGTGGTATGCCACTGCCGGAAAAGGGCGACGAGCGCCGGCGCGGAGAACTTCTCGCCGGCGCTTACAAAGTAGTCGTAATCGCGGGGCAGCAGCACCCGTGCCGTGACTCGTTGCGGGTGCCCGCGTGGCCGCAGGCCCACCTCGCACACCTCGACCAGGTCCCCGAACGCGCCCTCCTTCTTGATCGGCGGAAACGCAAGAGTCTGGTATTCGCGCGCAAATAGCGCGGTTCCGGTGGTGATGTTAACGGTCAGCGAAGCGGCGGACGCGCACTGGGGGGTGTCGCGATCCGCCAGGCGCGCCCCGCCACGCCGCGCGTCGGGATGCTCGGCAACGCGCGCCGCCAGGGCCATAGGGTCGATGTCAATGTTGGCCTCCGCGACCAGGAGAGCGGCGCGAGGGGCGGCGGGCGGGCCCCACGACGCTCTCTCAACTTTCACCCCCAGTCCCGTGCGTGGGTCCGAGCCGATACGCAGCGGGGCGAACAGGGCCACCGGCCCGGTCTGGCGCTCCAGGGCCGCCAGGACGCACGCGTACAGCGCCCGCCACAGAGTCGGGTTCTCCAGGGGCTCCAGCGGGGAGGCGGCCGGCGTCGTCGCGGCGCGGGCGGCCGCCACGACGGCCTGGACGGAGACGTCCGCGGAGCCGTAGAAATCCCGCAGCTCCGTCGCGGTGACGGAGACCTCCGCAAAGCGCGCGCGACCCTCCCCTGCGGCGTTGCGACATACAAAATACACCAGGGCGTGGAAGTACTCGCGAGCGCGGGGGGGCAGCCATACCGCGTAAAGGGTAATGGCGCTGACGCTCTCCTCCACCCACACGATATCTGCGGTGTCCATCGCACGGCCCCTAAGGATCACGGGCGGTCTGTGGGTCCCATGCTGCCGTGCCTGGCCGGGCCCGGTGGGTCGCGGAAACCGGTGACGGGGGGGGGGCGGTTTTTGGGGTTGGGGTGGGGGTGGGAAACGGCCCGGGTCCGGGGGCCAACTTGGCCCCTCGGTGCGTTCCGGCAACAGCGCCGCCGGTCCGCGGACGACCACGTACCGAACGAGTGCGGTCCCGAGACTTATAGGGTGCTAAAGTTCACCGCCCCCTGCATCATGGGCCAGGCCTCGGTGGGGAGCTCCGACAGCGCCGCCTCCAGGATGATGTCAGCGTTGGGGTTGGCGCTGGATGAGTGCGTGCGCAAACAGCGCCCCCACGCAGGCACGCGTAGCTTGAAGCGCGCGCCCGCAAACTCCCGCTTGTGGGCCATAAGCAGGGCGTACAGCTGCCTGTGGGTCCGGCAGGCGCTGTGGTCGATGTGGTGGGCGTCCAACACCCCACGATTGTCTGTTTGGTGAGGTTTTTAACGCGCCCCGCCCCGGGAAACGTCTGCGTGCTTTTGGCCATCTGCACGCCAAACAGTTCGCCCCAGATTATCTTGAACAGCGCCACCGCGTGGTCCGTCTCGCTAACGGACCCGCGCGGGGGACAGCCGCTTAGGGCGTCGGCGACGCGCTTGACGGCTTCCTCCGAGAGCAGAAGTCCGTCGGTTACGTTACAGTGGCCCAGTTCGAACACCAGCTGCATGTAGCGGTCGTAGTGGGGGGTCAGTAGGTCCAGCACGTCATCGGGGCCGAAGGTCCTCCCAGATCCCCCGGCCGCCGAGTCCCAATGCAGGCGCGCGGCCATGGTGCTGCACAGGCACAACAGCTCCCAGACGGGGGTTACGTTCAGGGTGGGGGGCAGGGCCACGAGCTCCAGCTCTCCGGTGACGTTGATCGTGGGGATGACGCCCGTGGCGTAGTGGTCATAGACCGCCGATATGGCGCTGCTGCGGGTGGCCATGGGAACGCGGAGACAGGCCTCCAGCAACGCCAGGTAAATAAACCGCGTGCGTCCCATCAGGCTGTTGAGGTTGCGCATGAGCGCGACAATTTCCGCCGGCGCGACATCGGACCGGAGGTATTTTTCGACGAAAAGACCCACCTCCTCCGTCTCGGCGGCCTGGGCCGGCAGCGACGCCTCGGGATCCCGGCACCGCAGCTCCCGTAGATCGCGCTGGGCCCTGAGGGCGTCGAAATGTACGCCCCGCAAAAACAGACAGAAGTCCTTTGGGGTCAGGGTATCGTCGTGTCCCCAGAAGCGCACGCGTATGCAGTTTAGGGTCAGCAGCATGTGAAGGATGTTAAGGCTGTCCGAGAGACACGCCAGCGTGCATCTCTCAAAGTAGTGTTTGTAACGGAATTTGTTGTAGATGCGCGACCCCCGCCCCAGCGACGTGTCGCATGCCGACGCGTCACAGCGCCCCTTGAACCGGCGACACAGCAGGTTTGTGACCTGGGAGAACTGCGCGGGCCACTGGCCGCAGGAACTGACCACGTGATTAAGGAGCATGGGCGTAAAGACGGGCTCCGAGCGCGCCCCGGAGCCGTCCATGTAAATCAGTAGCTCCCCCTTGCGGAGGGTGCGCACCCGTCCCAGGGACTGGTACACGGACACCATGTCCGGTCCGTAGTTCATGGGTTTTACGTAGGCGAACATGCCATCAAAGTGCAGGGGATGAAGCGGAGGCCCACGGTTACGACCGTCGTGTATATAACCACGCGGTATTGGCCCCACGTGGTCACGTCCCCGAGGGGGGTGAGCGAGTGAAGCAACAGCACGCGGTCCGTAAACTGACGGCAGAACCGGGCCACGATCTCCGCGAAGGAGACCGTCGACGAAAAAATGCAGATGTTATCGCCCCCGCCAAGGCGCGCTTCCAGCTCCCCAAAGAACGTGGCCCCCCGGGCGTCCGGAGAGGCGTCCGGAGACGGGCCGCTCGGCGGCCCGGGCGGGCGCAGGGCAGCCTGCAGGAGCTCGGTCCCCAGACGCGGGAGAAACAGGCACCGGCGCGCCGAAAACCCGGGCATGGCGTACTCGCCGACCACCACATGCACGTTTTTTTCGCCCCGGAGACCGCACAGGAAGTCCACCAACTGCGCGTTGGCGGTTGCGTCCATGGCGATGATCCGAGGACAGGTGCGCAGCAGGCGTAGCATTAACGCATCCACGCGGCCCAGTTGCTGCATCGTTGGCGAATAGAGCTGGCCCAGCGTCGACATAACCTCGTCCAGAACGAGGACGTCGTAGTTGTTCAGAAGGTTGGGGCCCACGCGATGAAGGCTTTCCACCTGGACGATAAGTCGGTGGAAGGGGCGGTCGTTCATAATGTAATTGGTGGATGAGAAGTAGGTGACAAAGTCGACCAGGCCTGACTCAGCGAACCGCGTCGCCAGGGTCTGGGTAAAACTCCGACGACAGGAGACGACGAGCACACTCGTGTCCGGAGAGTGGATCGCTTCCCGCAGCCAGCGGATCAGCGCGGTAGTTTTTCCCGACCCCATTGGCGCGCGGACCACAGTCACGCACCTGGCCGTCGGGGCGCTCGCGTTGGGGAAGGTGACGGGTCCGTGCTGCTGCCGCTCGATCGTTGTTTTCGGGTGAACCCGGGGCACCCATTCGGCCAAATCCCCCCCGTACAACATCCGCGCTAGCGATACGCTCGACGTGTACTGTTCGCACTCGTCGTCCCCAATGGGACGCCCGGCCCCAGAGGATCTCCCGACTCCGCGCCCCCCACGAAAGGCATGACCGGGGCGCGGACGGCGTGGTGGGTCTGGTGTGTGCAGGTGGCGACGTTTGTGGTCTCTGCGGTCTGCGTCACGGGGCTCCTCGTCCTGGCCTCTGTGTTCCGGGCACGGTTTCCCTGCTTTTACGCCACGGCGAGCTCTTATGCCGGGGTGAACTCCACGGCCGAGGTGCGCGGGGGTGTAGCCGTGCCCCTCAGGTTGGACACGCAGAGCCTTGTGGGCACTTATGTAATCACGGCCGTGTTGTTGTTGGCCGCGGCCGTGTATGCCGTGGTCGGCGCCGTGACCTCCCGCTACGACCGCGCCCTGGACGCGGGCCGCCGTCTGGCTGCGGCCCGCATGGCCATGCCGCACGCCACGCTGATCGCCGGAAACGTCTGCTCTTGGTTGCTGCAGATCACCGTCCTGTTGCTGGCCCATCGCACCAGCCAGCTGGCCCACCTGGTTTACGTCCTGCACTTTGCGTGTCTGGTGTATTTTGCGGCCCATTTTTGCACCAGGGGGGTCCTGAGCGGGACGTATCTGCGTCAGGTGCACGGCCTGATGGAGCCGGCCCCGACTCATCATCGCGTCGTTGGCCCGGCTCGAGCCGTGCTGACAAACGCCTTGCTGTTGGGCGTCTTCCTGTGCACGGCCGACGCCGCGGTATCCCTGAATACCATCGCCGCGTTCAACTTTAATTTTTCGGCCCCGGGCATGCTCATATGCCTGACCGTGCTGTTCGCCCTTCTCGTCGTATCGCTGTTGTTGGTGGTCGAGGGGGTGTTGTGTCACTACGTGCGCGTGTTGGTGGGCCCCCACCTGGGGGCCGTGGCCGCCACGGGCATCGTCGGCCTGGCATGCGAGCACTATTACACCAACGGCTACTACGTTGTGGAGACGCAGTGGCCGGGGGCCCAGACGGGAGTCCGCGTCGCCCTCGCCCTGGTCGCCGCCTTTGCCCTCGGCATGGCCGTGCTCCGCTGCACCCGCGCCTATCTGTATCACAGGCGGCACCACACCAAATTTTTTATGCGCATGCGCGACACGCGACACCGCGCACATTCCGCCCTCAAGCGCGTACGCAGTTCCATGCGCGGATCGCGAGACGGCCGCCACAGGCCCGCACCCGGCAGCCCGCCCGGGATTCCCGAATCCTTCGAAGACCCCTACGCGATCTCATACGGCGGCCAGCTCGACCGGTACGGAGATTCCGACGGGGAGCCGATTTACGACGAGGTGGCGGACGACCAAACCGACGTATTGTACGCCAAGATACAACACCCGCGGCACCTGCCCGACGACGAGCCCATCTATGACACCGTTGGGGGGTACGACCCCGAGCCCGCCGAGGACCCCGTGTACAGCACCGTCCGCCGTTGGTAGCTGTTTGGTTCCGTTTTAATAAACCGTTTGTGTTTAACCCGACCGTGGTGTATGTCTGGTGTGTGGCGTCCGATCCCGTTACTATCACCGTTCCCCCCAAACCCCGGCGATTGTGGGTTTTTTTAAAAACGACACGCGTGCGACCGTATACAGAACATTGTTGTTTTTTATTCGCTATCGGACATGGGGGGTGGAAACTGGGTGGCGGGGCAGGCGCCTCCGGGGGTTCGCCGGTGAGTGTGGCGCGAGGGGGATCCGACGAACGCAGGCGCTGTCTCCCCGGGGCCCGCGTAACCCCGCGCATATCCGGGGGCACGTAGAAATTACCTTCCTCTTCGGACTCGATATCCACGACGTCAAAGTCGTGGGCGGTCAGCGAGACGACCTCCCCGTCGTCGGTGATGAGGACGTTGTTTCGGCAGCAGCAGGGCCGGGTTTCCTTTTCCCCCGAGCCCATAGCTCGGCGAGCGTGTCGTCGAACGCCAGGCGGCTGCTTCGCTGTATGGCCTTATAGATCTCCGGATCGATGCGGACGGGGGTAATGATCAGGGCGATCGGAACGGCCTGGTTCGGGAGAATGGACGCCTTGCTGGGTCCTGCGGCCCCGAGAGCCCCGGCGCCGTCCTCCAGGCGGAACGTTACGCCCTCCTCCGCGCTAGTGCGGTGCCTGCCGATAAACGTCACCAGATGCGGGTGGGGGGGGCAGTCGGGGAAGTGGCTGTCGAGCACGTAGCCCGCACCAAGATCTGCTTAAAGTTCGGGGACGGGGGGTCGCGAAGACGGGCTCGCGGCGTACCAGATCCCCGGAGCTCCAGGACACGGGGGAGATGGTGTGGCGTCCGAGGTCGGGGGTGCCAAACAGAAGCACCTCCGAGACAACGCCGCTATTTAACTCCACCAAGGCCCGATCCGCGGCGGAGCACCGCCTTTTTTCGCCCGAGGCGTGGGCCTCTGACCAGGCCTGGTCTTGCGTGACGAGAGCCTCCTCCGGGCCGGGGACGCGCCCGGGCGCGAAGTATCGCACGCTGGGCTTCGGGATCGACCGGATAAATGCCCGGAACGCCTCCGGGGACCGGTGTGCCATCAAGTCCTCGTACGCGGAGGCCGTGGGGTCGCTGGGGTCCATGGGGTCGAAAGCGTACTTGGCCCGGCATTTGACCTCGTAAAAGGCCAGGGGGGTCTTGGGGACTGGGGCCAAGTAGCCGTGAATGTCCCGAGGACAGACGAGAATATCCAGGGACGCCCCGACCATCCCCGTGTGACCGTCCATGAGGACCCCACACGTATGCACGTTCTCTTCGGCGAGGTCGCCGGGTTCGTGGAAGATAAAGCGCCGCGTGTCGGCGCCGGCCTCGCCGCCGTCGTCCGCGCGGCCCACGCAGTAGCGAAACAGCAGGCTTCGGGCCGTCGGCTCGTTCACCCGCCCGAACATCACCGCCGAAGACTGTACATCCGGCCGCAGGCTGGCGTTGTGCTTCAGCCACTGGGGCGAGAAACACGGACCCTGGGGGCCCCAGCGGAGGTGGTATGCGGTCGTGAGGCCGCGGAGCAGGGCCCATAGCTGGCAGTCGGCCTGGTTTTGCGTGGCCGCCTCGTAAAACCCCATGAGGGGCCGGGGCGCCACGGCGTCCGCGGCGGCCGGGGGCCCGCGGCGCGTCAGGCGCCATAGGTGCCGGCCGAGTCCGCGGTCCACCATACCCGCCTCCTCGAGGACCACGGCCAGGGAACACAGATAATCCAGGCGGGCCCCCCCCCTCTCCCCTCTCCCCCCCTCTCCCCTGCTCTTTCCCCGCGACACCCGACGCTGGGGGGCGTGGCTGCCGGGAGGGGCCGCGTATGGGCGGGCCTACTCGGTCTCCCGCCCCCCCGAACCGCCCCGCCGGCTTTGCCCCCCTTTGATCCCCTGCTACCCCCACCCCGTGCTCGTGGTGCGGGGTGGGGGGATGTGGGCGGGGGTGCGCGGGAGGTGTCGGTGGTGGGGGTGGTGGTGGTGGTGGTAGTAGGAATGGTGGTGGGGGGGAGGGCGCTGGTTGGTCAAAAAAGGGAGGGACGGGGGCCGGCAGACCGACGGCGACAACGCTCCCCGGCGGCCGGGTCGCGGCCTTACGGCGGCCCGCCCGCGCCCCCCCCCCCGGGCCGTGTCCTTGCTTTCCCCCCGTCTCCCCCCTTTTGCGTGGCCGCCTCGTAAACCCCCAGAGGGGCCGGGGCGCCACGGCGTCCGCGGCGGCCGGGGGCCCGCGGCGCGTCAGGCGCCATAGGTGCCGGCCGAGTCCGCGGTCCACCATACCCGCCTCCTCGAGGACCACGGCCAGGGAACACAGATAATCCAGGCGGGCCCAGAGGGGACCGATGGCCAGAGGGGCGCGGACGCCGCGCAGCAACCCGCGCAGGTGGCGCTCGAACGTCTCGGCTAGTATATGGGAGGGCAGCGCGTTGGGGATCACCGACGCCGACCACATAGAGTCAAGGTCCGGGGAGTCGGGATCGGCGTCCGGGTCGCGGGCGTGGGTGCCCCCAGGAGATAGCGGAATGTCTGGGGTCGGAGGCCTGAGGCGTCAGAAAGTGCCGGCGACGCGGCCCGGGGCTTTTCGTCTGCGGTGTCGGTGGCGTGCTGATCACGTGGGGGGTTAACGGGCGAATGGGGAGCTCGGGTCCACAGCTGACGTCGTCTGGGGTGGGGGGGGCAGGGGACGGAAGGTGGTTGTTAGCGGAAGACTGTTAGGGCGGGGGCGCTTGGGGGGGCTGTCGGGGCCACGAGGGGTGTCCTCGGCCAGGGCCCAGGAACGCTTAGTCACGGTGCGTCCCGGCGGACATGCTGGGCCTCCCGTGGACTCCATTTCCGAGACGACGTGGGGGAGCGGTGGTTGAGCGCGCCGCCGGGTGAACGCTGATTCTCACGACAGCGCGTGCCGCGCGCACGGGTTGGTGTGACACAGGCGGGCCCGCCTCCTCGAGGACCACGGCCAGGGAACACAGATAATCCAGGCGGGCCCAGAGGGGACCGATGGCCAGAGGGGCGCGGACGCCGCGCAGCAACCCGCGCAGGTGGCGCTCGAACGTCTCGGCTAGTATATGGGAGGGCAGCGCGTTGGGGATCACCGACGCCGACCACATAGAGTCAAGGTCCGGGGAGTCGGGATCGGCGTCCGGGTCGCGGGCGTGGGTGCCCCCAGGAGATAGCGGAATGTCTGGGGTCGGAGGCCCTGAGGCGTCAGAAAGTGCCGGCGACGCGGCCCGGGGCTTTTCGTCTGCGGTGTCGGTGGCGTGCTGATCACGTGGGGGGTTAACGGGCGAATGGGAGCTCGGGTCCACAGCTGACGTCGTCTGGGGTGGGGGGGGCAGGGGACGGAAGGTGGTTGTTAGCGGAAGACTGTTAGGGCGGGGGCGCTTGGGGGGGCTGTCGGGGCCACGAGGGGTGTCCTCGGCCAGGGCCCAGGAACGCTTAGTCACGGTGCGTCCCGGCGGACATGCTGGGCCTCCCGTGGACTCCATTTCCGAGACGACGTGGGGGAGCGGTGGTTGAGCGCGCCGCCGGGTGAACGCTGATTCTCACGACAGCGCGTGCCGCGCGCACGGGTTGGTGTGACACAGGCGGGACACCAGCACCAGGAGAGGCTTAAGCTCGGGAGGCAGCGCCACCGACGACAGTATCGCCTTGTGTGTGTGCTGGTAATTTATACACCGATCCGTAAACGCGCGCCGAATCTTGGGATTGCGGAGGTGGCGCCGGATGCCCTCTGGGACGTCATACGCCAGGCCGTGGGTGTTGGTCTCGGCCGAGTTGACAAACAGGGCTGGGTGCAGCACGTGGCGATAGGCGAGCAGGGCCAGGGCGAAGTCCAGCGACAGCTGGTTGTTGAAATACTGGTAACCGGGAAACCGGGTCACGGGTACGCCCAGGCTCGGGGCGACGTACACGCTAACCACCAACTCCAGCAGCGTCTGGCCAAGGGCGTACAGGTCAACCGCTAACCCGACGTCGTGCTTCAGGCGGTGGTTGGTAAATTCGGCCCGTTCGTTGTTAAGGTATTTCACCAACAGCTCCGGGGGCTGGTTATACCCGTGACCCACCAGGGGTGAAAGTTGGCTGTGGTTAGGGCGGTGGGCATGCCAAACATCCGGGGGGACTTGAGGTCCGGCTCCTGGAGGCAAAACTGCCCCCGGGCGATCGTGGAGTTGGAGTTGAGGGTGACGAGGCTAAAGTCGGCGAGGACGGCCCGCCGGAGCGAGACGGCGTCCGACCGCAGCATGACGAGGATGTTGGCGCGTGAATCGGGTGGCTCCCCAGGTGGTGTTTAAAAACACAACGGCGCGGGCCAGCTCCGTGAAGCACTGGTGGAGGGCCGTCGAGACCGAGGGGTTTGTTGTGCGCAGGGACGCCAGTTGGCCGATATACTTACCGAGGTCCATGTCGTACGCGGGGAACACTATCTGTCGTTGTTGCAGCGAGAACCCGAGGGGCGCGATGAAGCCGCGGATGTTGTGGGTGCGGCCGGCGCGTAGAGCGCACTCCCCGACCAACAGGGTCGCGATGAGCTCAACGGCAAACCACTCCTTTTCCTTTATGGTCTTAACGGCAAGCTTATGTTCGCGAATCAGTTGGACGTCGCCGTATCCCCCAGACCCCCCGAAGCTTCGGGCCCCGGGGATCTCGAGGGTCGTGTAGTGTAGGGCGGGGTTGATGGCGAACACGGGGCTGCATAGCTTGCGGATGCGCGTGAGGGTAAGGATGTGCGAGGGGGACGAGGGGGGTGCGGTTAACGCCGCCTGGGATCTGCGCAGGGGCGGGCGGTTCAGTTGGCCGCCGTACCGGGCGGCTCGGGGGACGCGCGGCGATGAGACGAGCGGCTCATTCGCCATCGGGATAGTCCCGCGCGAAGCCGCTCGCGGAGGCCGGATCGGTGGCGGGACCCGTGGGAGGAGCGGGAGCCGGCGGCGTCCTGGAGAGAGGGGCCGCTGGGGCGCCCGGAGGCCCCGTGTGGGTTGGGTGTATGTAGGATGCGAGCCAATCCTTGAAGGACTGTTGGCGTGCATTGGGGGTGAGGTGAGAGGAAAAATGACCAGCAGGTCGCTGTCTGCGGGACTCATCCATCCTTCGGCCAGGTCGCCGTCTTCCCACAGAGAAGCGTTGGTCGCTGCTTCCTCGAGTTGCTCCTCCTGGTCCGCAAGACGATCGTCCACGGCGTCCAGGCGCTCACCAAGCGCCGGATCGAGGTACCGTCGGTGTGCGGTTAGAAAGTCACGACGCGCCGCTTGCTCCTCCACGCGAATTTTAACACAGGTCGCGCGCTGTCGCATCATCTCTAAGCGCGCGCGGGACTTTAGCCGCGCCTCCAATTCCAAGTGGGCCGCCTTTGCAGCCATAAAGGCGCCAACAAACCGAGGATCTTGGGTGCGACGCCCCCCGGTGCAGCGCAGGGTCTGGTCCTTGTAAATCTCGGCTCGGAGGTGCGTCTCGGCCAGGCGTCGGCGCAGGGCCGCGTGGGCGGCATCTCGGTCCATTCCGCCCCCTGCGGGCGACCCGGGGGGTGCTCTGATAGTCTCGCGTGCCCAAGGCCCGTGATCGGGGTACTTCGCCGCCGCGACCCGCCACCCGGTGTGCGCGATGTTTGGTCAGCAGCTGGCGTCCGACGTCCAGCAGTACCTGGAGCGCCTCGAGAAACAGAGGCAACTTAAGGTGGGCGCGGACGAGGCGTCGGCGGGCCTCACAATGGGCGGCGATGCCCTACGAGTGCCCTTTTTAGATTTCGCGACCGCGACCCCCAAGCGCCACCAGACCGTGGTCCCGGGCGTCGGGACGCTCCACGACTGCTGCGAGCACTCGCCGCTCTTCCGGCCGTGGCGCGGCGGCTGCTGTTTAATAGCCTGGTGCCGGCGCAACTAAAGGGGCGGGAGGGCGGGGGCGACCACACGGCCAAGCTGGAATTCCTGGCCCCCGAGTTGGTACGGGCGGTGGCGCGACTGCGGTTTAAGGAGTGCGCGCCGGCGGACGTGGTGCCTCAGCGTAACGCCTACTATAGCGTTCTGAACACGTTTCAGGCCCTCCACCGCTCCGAAGCCTTTCGCCAGCTGGTGCACTTTGTGCGGGACTTTGCCCAGCTGCTTAAAACCTCCTTCCGGGCCTCCAGCCTCACGGAGACCACGGGCCCCCCAAAAAAACGGGCCAAGGTGGACGTGGCCACCCACGGCCGGACGTACGGCACGCTGGAGCTGTTCCAAAAAATGATCCTTATGCACGCCACCTACTTTCTGGCCGCCGTGCTCCTCGGGGACCACGCGGAGCAGGTCAACACGTTCCTGCGTCTCGTGTTTGAGATCCCCCTGTTTAGCGACGCGCCGTGCGCCACTTCCGCCAGCGCGCCACCGTGTTTCTCGTCCCCCGGCGCCACGGCAAGACCTGGTTTCTAGTGCCCCTCATCGCGCTGTCGCTGGCCTCCTTTCGGGGGATCAAGATCGGCTACACGGCGCACATCCGCAAGGCGACCGAGCCGGTGTTTGAGGAGATCGACGCCTGCCTGCGGGGCTGGTTCGGTTCGGCCCGAGTGGACCACGTTAAAGGGGAAACCATCTCCTTCTCGTTTCCGGACGGGTCGCGCAGTACCATCGTGTTTGCCTCCAGCCACAACACAAACGTAAGTCCTCTTTTCTTTCGCATGGCTCTCCCAAGGGGCCCCGGGTCGACCCGACCCACACCCACCCACCCACCCACATACACACACAACCAGACGCGGGAGGAAAGTCGGCCCCGTGGGCACTGATTTTTATTCGGGATCGCTTGAGGAGGCCCGGGCAACGGCCCGGGCAACGGTGGGGCAACTCGTAGCAAATAGGCGACTGATGTACGAAGAGAAGACACACAGGCGCCACCCGGCGCTGGTCGGGGGGATGTTGTCCGCGCCGCACCGTCCCCCGACGACCTCTTGCAGACGGTCCGTGATGCAAGGACGGCGGGGGGCCTGCAGCAGGGTGACCGTATCCACGGGATGGCCAAAGAGAAGCGGACACAGGCTAGCATCCCCCTGGACCGCCAGGGTACACTGGGCCATCTTGGCCCACAGACACGGGGCGACGCAGGGACAGGACTCCGTTACGACGGAGGAGAGCCACAGTGCGTTGGCGGAATCGATGTGGGGCGGCGGGGCGCAGGACTCGCAGCCCCCCGGGTGGTTGGTGATCCTGGCCAGGAGCCATCCCAGATGGCGGGCCCTGCTTCCCGGTGGACAGAGCGACCCCAGGTCGCTGTCCATGGCCCAGCAGTAGATCTGGCCGCTGGGGAGGTGCCACCAGGCCCCCGGGCCCAAGGCGCAACACGCGCCCGGCTCCGGGGGGGTCTTCGCGGGGACCAGATACGCGCCATCCAGCTCGCCGACCACTGGCTCCTCCGCGAGCTGTTCGGTGGTTGGGTCGGGGGTTTCCTCCGGGGGGGTGGCCGCCCGTATGCGGGCGAACGTGAGGGTGCACAGGAGCGGGGTCAGGGGGTGCGTCACGCTCCGGAGGTGGACGATCGAGCAGTAGCGGCGCTCGCGGTTAAAGAAAAAGAGGGCAAAGAAGGTGTTCGGGGGCAACCGCAGCGCCTTGGGGGCGTCAGAAAGAAAAATCTCGCAGAAGAGGGGGCCCGGGGTCTGGGTTAGGAAGGGCCACCTGACACAGAGGCTCGGTGAGGACCGTTAGACACCGAAAGATCTTGAGCCGCTCGTCCACCCGAACGACGCGCCACACAAAGACGGAGTTGACAATGCGCGCGATAGAGTCGACGTCCGTCCCCAGGGCGTCGACTCTGTCGCGCGTGCCGCGAGCTCCGACCCGGGAATCCGGCCGGGGCAAGGTCCCCGGGGGACCAGGCGGCGCCAGGGGCCGCCGGGGTCCCAGCTGCGCCATGCCGGGGGCGGGGGGAGGGCAAACCCCAGAGGCGGGGGCCAACGGCGCGGGGAGGAGTGGGTGGGCGAGGTGGCCGGGGGAAGGCGCCCGCTAGCGAGAACGGCCGTTCCCGGACGACACCTTGCGACAAAACCTAAGGACAGCGGCCCGCGCGACGGGGTCCGAGAGGCTAAGGTAGGCCGCGATGTTAATGGTGAACGCAAAGCCGCCGGGAAAGACAACTATGCCACAGAGGCGGCGATTAAACCCCAGGCAGAGGTAGGCGTAGCTTTCCCCGGGCAGGTATTGCTCGCAGACCCTGCGTGGGGCTGTGGAGGGGACGGCCTCCATGAAGCGACATTTACTCTGCTCGCGTTTACTGACGTCATCATCCATCGCCACGGCGATTGGACGATTGTTAAGCCGCAGCGTGTCTCCGCTTGTGCTGTAGTAGTCAAAAACGTAATGGCCGTCGGAGTCGGCAAAGCGGGCCGGGAGGTCGTCGCCGAGCGGGACGACCCGCCGCCCCCGACCGCCCCGTCCCCCCAGGTGTGCCAGGACGGCCAGGGCATACGCGGTGTGAAAAAAGGCGTCGGGGGCGGTCCCCTCGACGGCGCGCATCAGGTTCTCGAGGAGAATGGGGAAGCGCCTGGTCACCTCCCCCAGCCACGCGCGTTGGTCGGGGCCAAAGTCATAGCGCAGGCGCTGTGAGATTCGAGGGCCGCCCTGAAGCGCGGCCCGGATGGCCTGGCCCAGGGCCCGGAGGCACGCCAGATGTATGCGCGCAGTAAAGGCGACCTCGGCGGCGATGTCAAAGGGCGGCAGGACGGGGCGCGGGTGGCGCAGGGGCACCTCGAGCGCGGGAAAGCGGAGCAGCAGCTCCGCCTGCCCAGCGGGAGACAGCTGGTGGGGGCGCACGACGCGTTCTGCGGCGCAGGCCTCGGGTCGGGGCCGTGGCCAGCGCCGAGGACAGCAGCGGAGGGCGGGCGCGTCGCCCGCCCCACGCCACGGAGTTCTCGTAGGAGACGACGACGAAGCGCTGCTTGGTTCCGTAGTGGTGGCGCAGGACCACGGAGATAGAACGACGGCTCCACAGCCAGTCCGGCCGGTCGCCGCCGGCCAGGGCTTCCCATCCGCGATCCAACCACTCGACCAGCGACCGCGGCTTTGCGGTACCAGGGGTCAGGGTTAGAACGTCGTTCAGGATGTCCTCGCCCCCGGGCCCGTGGGGCACTGGGGCCACAAAGCGGCCCCCGCCTGGGGGCTCCAGACCCGCCAACACCGCATCTGCGTCAGCCGCCCCCATGGCGCCCCCGCTGACGGCCTGGTGAACCAGGGCGCCCTGGCGGAGCCCCGATGCAACGCCACAGGCCGCACGCCCGGTCCGAGCGCGGACCGGGTGGCGGCGGGTGACGTCCTGCACTGCCCGCTGAACCAACGCGAGGATCTCCTCGTTCTCCTGCGCGATGGACACGTCCTGGGCCGCGGTCGTGTCGCCGCCGGGGGCCGTCAGCTGCTCCTCCGGGGAGATGGGGGGGTCGGACGCCCCGACGATGGGCGGGTCTGCGGGCGCCCCCGCGTGGGGCCGGGCCAAGGGCTGCGGACGCGGGGACGCGCTTTCCCCCAGACCCATGGACAGGTGGGCCGCAGCCTCCTTCGCGGCCGGCGGGGCGGCGGCGCCAAGCAGAGCGACGTAGCGGCACAAATGCCGACAGACGCGCATGATGCGCGTGCTGTCGGCCGCGTAGCGCGTGTTGGGGGGGACGAGCTCGTCGGAACTAAACAGAATCACGCGGGCACAGCTCGCCCCCGAGCCCCACGCAAGGCGCAGCGCCGCCACGGCGTACGGGTCATAGACGCCCTGTGCGTCACACACCACGGGCAAGGAGACGAACAACCCCCCGGCGCTGGACGCACGCGGAAGGAGGCCAGGGTGTGCCGGCACGACGGGGGCCAGAAGCTCCCCCACCGCATCCGCGGGCACGTAGGCGGCAAACGCCGTGCACCACGGGGTACAGTCGCCGGTGGCATGAGCCCGAGTCTGGATTTCGACCTGGAAGTTTGCGGCCGTCCCGAGTCCGGGGCGGCCGCGCATCAGGGCGGCCAGAGGGATTCCCGCGGCCGCCAGGCACTCGCTGGATATGATGACGTGAACCAAAGACGAGGGCCGACCCGGGACGTGGCCGAGATCGTACTGGACCTCGTTGGCCAAGTGCGCGTTCATGGTTCGGGGGTGGGTGTGGGTGTGTAGGCGATGCGGGTCCCCCGAGTCCGCGGGAAGGGCGCGGGTTTGGCGCGCGTATGCGTATTCGCCAACGGAGGCGTGCGTGCTTATGCGCGGCGCGTTTCTTCTGTCTCCAGGGAATCCGAGGCCAGGACTTTAACCTGCTCTTTGTCGACGAGGCCAACTTTATTCGCCCGGATGCGGTCCAGACGATTATGGGCTTTCTCAACCAGGCCAACTGCAAGATTATCTTCGTGTCGTCCACCAACACCGGGAAGGCCAGTACGAGCTTTTTGTACAACCTCCGCGGGGCCGCCGACGAGCTTCTCAACGTGGTGACCTATATATGCGATGATCACATGCCGCGGGTGGTGACGCACACAAACGCCACGGCCTGTTCTTGTTATATCCTCAACAAGCCCGTTTCAGCACGATGGACGGGGCGGTTCGCCGGACCGCCGATTTGTTTCTGGCCGATTCCTTCATGCAGGAGATCATCGGGGGCCAGGCCAGGGAGACCGGCGACGACCGGCCCGTTCTGACCAAGTCTGCGGGGGAGCGGTTTCTGTTGTACCGCCCCTCGACCACCACCAACAGCGGCCTCATGGCCCCCGATTTGTACGTGTACGTGGATCCCGCGTTCACGGCCAACACCCGAGCCTCCGGGACCGGCGTCGCTGTCGTCGGGCGGTACCGCGACGATTATATCATCTTCGCCCTGGAGCACTTTTTTCTCCGCGCGCTCACGGGCTCGGCCCCCGCCGACATCGCCCGCTGCGTCGTCCACAGTCTGAGGTAGGGCCAGGCCCTGCATCCCGGGGCGTTTCGCGGCGTCCGGGTGGCGGTCGAGGGAAATAGCAGCCAGGACTCGGCCGTCGCCATCGCCACGCACGTGCACACAGAGATGCACCGCCTATGGCCTCGGAGGGGGCCGACGCGGGCTCGGGCCCCGAGCTTCTCTTCTACCACTGCGAGCCTCCCGGGAGCGCGGTGCTGTACCCCTTGGTCCTGCTCAACAAACAGAAGACGCCCGCCTTTGAACACTTTATTAAAAAGTTTAACTCCGGGGGCGTCATGGCCTCCCAGGAGATCGTTTCCGCGACGGTGCGCCTGCAGACCGACCCGGTCGAGTATCTGCTCGAGCAGCTGAATAACCTCACCGAAACCGTCTCCCCCAACACGGACGTCCGTACGTATTCCGGAAAACGGAACGGCGCCTCGGATGACCTTATGGTCGCCGTCATTATGGCCATCTACCTTGCGGCCCAGGCCGGACCTCCGCACACATTCGCTCCCATCACACGCGTTTCGTGAGCGCCCAATAAACACACCCAGGTATGCTACGCACGACCACGGTGTCGCCTGTTAAGGGGGGGGGAAGGGGGTGTTGGCGGGAAGCGTGGGAACACGGGGGATTCTCTCACGACCGGCACCAGTACCACCCCCCTGTGAACACAGAAACCCCAACCCAAATCCCATAAACATACGACACCCGGCATATTTTGGAATTTCTTCGGTTTTTATTTATTTAGGTATGCTGGGGTTTCTCCCTGGATGCCCACCCCCACCCCCCCCGTGGGTCTAGCCGGGCCTTAGGGATAGCGTATAACGGGGGCCATGTCTCCGGACCGCACAACGGCCGCGCCGTCAAAGGTGCACACCCGAACCACGGGAGCCAGGGCCAAGGTGTCTCCTAGTTGGCCCGCGTGGGTCAGCCAGGCGACGAGCGCCTCGTAGAGCGGCAGCCTTCGCTCTCCATCCTGCATCAGGGCCGGGGCTTCGGGGTGAATGAGCTGGGCGGCCTCCCGCGTGACACTCTGCATCTGCAGGAGAGCGTTCACGTACCCGTCCTGGGCACTTAGCGCAAAGAGCCGGGGGATTAGCGTAAGGATGATGGTGGTTCCCTCCGTGATCGAGTAAACCATGTTAAGGACCAGCGATCGCAGCTCGGCGTTTACGGGGCCGAGTTGTTGGACGTCCGCCAGCAGCGAGAGGCGACTCCCGTTGTAGTACAGCACGTTGAGGTCTGGCAGCCCTCCGGGGTTTCTGGGGCTGGGGTTCAGGTCCCGGATGCCCCTGGCCACGAGCCGCGCCACGATTTCGCGCGCCAGGGGCGATGGAAGCGGAACGGGAAACCGCAACGTGAGGTCCAGCGAATCCAGGCGCACGTCCGTCGCTTGGCCCTCGAACACGGGCGGGACGAGGCTGATGGGGTCCCCGTTACAGAGATCTACGGGGGAGGTGTTGCGAAGGTTAACGGTGCCGGCGTGGGTGAGGCCCACGTCCAGGGGGCAGGCGACGATTCGCGTGGGAAGCACCCGGGTGATGACCGCGGGGAAGCGCCTTCGGTACGCCAGCAACAGCCCCAACGTGTCGGGACTGACGCCTCCGGAGACGAAGGATTCGTGCGCCACGTCGGCCAGCGTCAGTTGCCGGCGGATGGTCGGAGGAATACCACCCGCCCTTCGCAGCGCTGCAGCGCCGCCGCATCGGGGCGCGAGATGCCCGAGGGTATCGCGATGTCAGTTTCAAAGCCGTCCGCCAGCATGGCGCCGATCCACGCGGCAGGGAGTGCAGTGGTGGTTCGGGTGGCGGGAGGAGCGCGGTGGGGGTCAGCGGCGTAGCAGAGACGGGCGACCAACCTCGCATAGGACGGGGGGTGGGTCTTAGGGGGTTGGGAGGCGACAGGGACCCCAGAGCATGCGCGGGGAGGTCTGTCGGGCCCAGACGCACCGAGAGCGAATCCGCCATGGGCCCGGCCTGGGTTTTATGGGGCCCGGCCCTCGGAATCGCGGCTTGTCGGCGGGGGCAAAGGGGGCGGGGCTAGGGGGCTTGCGGGAACAGAGACGGGTGGGGTAAAAGAATCGCACTACCCCAAGGAAGGGCGGGGCGGTTTATTACAGAGCCAGTCCCTTGAGCGGGGATGCGTCATAGACGAGATACTGCGCGAAGTGGGTCTCCCGCGCGTGGGCTTCCCCGTTGCGGGCGCTGCGGAGGAGGGCGGGGTCGCTGGCGCAGGTGAGCGGGTAGGCCTCCTGAAACAGGCCACACGGGTCCTCCACGAGTTCGCGGCACCCCGGGGGGCGCTTAAACTGTACGTCGCTGGCGGCGGTGGCCGTGGACACCGCCGAACCCGTCTCCACGATCAGGCGCTCCAGGCAGCGATGTTTGGCGGCGATGTCGGCCGACGTAAAGAACTTAAAGCAGGGGCTGAGCACCGGCGAGGCCCCGTTGAGGTGGTAGGCCCCGTTATAGAGCAGGTCCCCGTACGAAAATCGCTGCGACGCCCACGGGTTGGCCGTGGCCGCGAAGGCCCGGGACGGGTCGCTCTGGCCGTGGTCGTACATGAGGGCGGTGACACCCCCTCCTTGCCCCCGCGTAAACGCCCCCGGGGCGCGCCCCGGGGGGTTGCGGGGCCGGCGGAAGTAGTTGACGTCGGTCGACACGGGGGTGGCGATAAACTCACACACGGCGTCCTGGCCGTGGTCCATCCCTGCGCGCCGCGGCCCCTGGGCGCACCCGAACACGGGGACGGGCTGGGCCGGCCCCAGGCGGTTTCCCGCCACGACCGCGTTCCGCAGGTACACGGCTGCCGCGTTGTCCAGTAGAGGGGGAGCCCCGCGGCCCAGGTAAAAGTTTTGGGGAAGGTTGCCCATGTCGGTGACGGGGTTGCGGACGGTTGCCGTGGCCACGACGGCGGTGTAGCCCACGCCCAGGTCCACGTTCCCGCGCGGCTGGGTGAGCGTGAAGTTTACCCCCCCGCCAGTTTCATGCCGGGCCACCTGGAGCTGGCCCAGGAAGTACGCCTCCGACGCGCGCTCCGAGAACAGCACGTTCTCAGTCACAAAGCGGTCCTGTCGGACGACGGTGAACCCAAACCCGGGATGGAGGCCCGTCTTGAGCTGATGATGCAAGGCCACGGGACTGATCTTGAAGTACCCCGCCATGAGCGCGTAGGTCAGCGCGTTCTCCCCGGCCGCGCTCTCGCGGACGTGCTGCACGACGGGCTGTCGGATCGACGAAAAGTAGTTGGCCCCCAGAGCCGGGGGGACCAGGGGGACCTGCCGCGACAGGTCGCGCAGGGCCGGGGGGAAATTGGGCGCGTTCGCCACGTGGTCGGCCCCGGCGAACAGCGCGTGGACGGGGAGGGGGTAAAAATAGTCGCCATTTTGGATGGTATGGTCCAGATGCTGGGGGGCCATCAGCAGGATTCCGGCGTGCAACGCCCCGTCGAATATGCGCATGTTGGTGGTGGACGCGGTGTTGGCGCCCGCGTCGGGCGCCGCCGAGCAGAGCAGCGCCGTTGTGCGTTCGGCCATGTTGTGGGCCAGCACCTGCAGCGTGAGCATGGCGGGCCCGTCCACTACCACGCGCCCGTTGTGAAACATGGCGTTGACCGTGTTGGCCACCAGATTGGCCGGGTGCAGGGGGGGCGCGGGGTCCGTCACGGGGTCGCTGGGGCAATCCTCGCCGGGGGTGATCTCCGGGACCACCATGTTCTGCAGGGTGGCGTATACGCGGTCGAAGCGAACCCCCGCGGTGCAGCAGCGGCCCCGCGAGAAGGCGGGCACCATCACGTAGTAGTAAATCTTGTGGTGCACGGTCCAGTCCGCCCCCCGGTGCGCCGGTCGTCCGCGGCGTCCGCGGCTCGGGCCTGGGTGTTGTGCAGCAGCTGGCCGTCGTTGCGGTTGAAGTCCGCGGTCGCCACGTTACACGCCGCTGCGTACACGGGGTCGTGGCCCCCCGCGCTAACCCGGCAGTCGCGATGGCGGTCCAGGGCCGCGCGCCGCATCAGGGCGTCGCAGTCCCACACGAGGGGTGGCAGCAGCGCCGGGTCTCGCATTAGGTGATTCAGTTCGGCTTGCGCCTGCCCGCCCAGTTCCGGGCCGGTCAGGGTAAAGTCATCAACCAGCTGGGCCAGGGCCTCGACGTGCGCCACCAGGTCCCGGTACACGGCCATGCACTCCTCGGGAAGGTCTCCCCCGAGGTAGGTCACGACGTACGAGACCAGCGAGTAGTCGTTCACGAACGCCGCGCACCGCGTGTTGTTCCAGTAGCTGGTGATGCACTGGACCACGAGCCGGGCCAGGGCGCAGAAGACGTGCTCGCTGCCGTGTATGGCGGCCTGCAGCAGGTAAAACCCGCCGGGTAGTTGCGGTCTTCGAACGCCCCGCGAACGGCGGCGATGGTGGCGGGGGCCATGGCGTGGCGTCCCACCCCCAGCTCCAGGCCCCGGGCGTCCCGGAACGCCGCCGGACATAGCGCCAGGGGCAAGTTGCCGTTCACCACGCGCCAGGTGGCCTGGATCTCCCCCGGGCCGGCCGGGGGAACGTCCCCCCCCGGCAGCTCCACGTCGGCCACCCCCACGAAGAAGTCGAACGCGGGGTGCAGCTCAAGAGCCAGGTTGGCGTTGTCGGGCTGCATAAACTGCTCCGGGGTCATCTGGCCTTCCGCGACCCATCGGACCCGCCCGTGGGCCAGGCGCTGCCCCCAGGCGTTCAAAAACAGCTGCTGCATGTCTGCGGCGGGGCCGGCCGGGGCCGCCACGTACGCCCCGTACGGATTGGCGGCTTCGACGGGGTCGCGGTAAGGCCCCCGACCGCCGCGTCAACGTTCATCAGCGAAGGGTGGCACACGGTCCCGATCGCGTGTTCCAGAGACAGGCGCAGCACCTGGCGGTCCTTCCCCCAAAAAAACAGCTGGCGGGGCGGGAAGGCGCGGGGATCCGGGTGGCCGGGGGCGGGGACTAGGTCCCCGGCGTGCGCGGCAAACCGTTCCATGACCGGATTGAACAGGCCCAGGGGCAGGACGAACGTCAGGTCCATGGCGCCCACCAGGGGGTAGGGAACGTTGGTGGCGGCGTAGATGCGCTTCTCCAGGGCCTCCAAAAAGATCAGCTTCTCGCCGATGGACACCAGATCCGCGCGCACGCGCGTCGTCTGGGGGGCGCTCTCGAGCTCGTCCAGCGTCTGCCGGTTCAGGTCGAGCTGCTCCTCCTGCATCTCCAGCAGGTGGCGGCCCACGTCGTCCAGACTTCGCACGGCCTTGCCCATCACGAGCGCCGTGACCAGGTTGGCCCCGTTCAGGACCATCTCGCCGTACGTCACCGGCACGTCGGCTTCGGTGTCCTCCACTTTCAGGAAGGACTGCAGGAGGCGCTGTTTGATCGGGGCGGTGGTGACGAGCACCCCGTCGACCGGACGCCCGCGCGTGTCGGCATGCGTCAGACGGGGCACGGCCATGGAGGGCTGCGTGGCCGTGGTGAGGTCCACGAGCCAGGCCTCGACGGCCTCCCGGCGGTGGCCCGCCTTGCCCAGGAAAAAGCTCGTCTCGCAGAAGCTTCGCTTTAGCTCGGCGACCAGGGTCGCCCGGGCCACCCTGGTGGCCAGGCGGCCGTTGTCCAGGTATCGTTGCATCGGCAACAACAAAGCCAGGGGCGGCGCCTTTTCCAGCAGCACGTGCAGCATCTGGTCGGCCGTGCCGCGCTCAAACGCCCCGAGGACGGCCTGGACGTTGCGAGCGAGTTGTTGGATGGCGCGCAACTGGCGATGCGCGCTGATACCCGTCCCGTCCAGGGCCTCCCCCGTGGCAGGGCGATGGCCTCGGTGGCCAGGCTGAAGGCGGCGTTCAGGGCCCGGCGGTCGATAATCTTGGTCATGTAATTGTGTGTGGGTTGCTCGATGGGGTGCGGGCCGTCGCGGGCAATCAGCGGCTGGTGGACCTCGAACTGTACGCGCCCCTCGTTCATGTAGGCCAGCTCCGGAAACTTGGTACACACGCACGCCACCGACAACCGCGCTCCAGAAAGCGCACGAGCGACAGGGTGTTGCAATACGACCCCAACAGGGCGTCGAACTCGACGTCATACAGGCTGTTTGCATCGGAGCGCACGCGGGAAAAAAAATCGAACAGGCGTCGATGCGACGCCACCTCGATCGTGCTAAGGAGGGACCCGGTCGGCACCATGGCCGCGGCATACCGGTATCCCGGAGGGTCGCGGTTGGGAGCGGCCATGGGGTCGCGTGGAGATCGGCTGTCTCTAGTGATATTGGCCCGGGGAGGCTAAGATCCACCCCAACGCCCGGCCACCCGTGTACGTGCCCGACGGCCCAAGGTCCACCGAAAGACACGACGGGCCCGGACCCAAAAAGGCGGGGGATGCTGTGTGAGAGGCCGGGTGTCGGTCGGGGGGGAAAGGCACCGGGAGAAGGCTGCGGCCTCGTTCCAGGAGAACCCAGTGTCCCCAACAGACCCGGGGACGTGGGATCCCAGGCCTTATATACCCCCCCCGCCCCACCCCCGTTAGAACGCGACGGGTGCATTCAAGATGGCCCTGGTCCAAAAGCGTGCCAGGAAGAAATTGGCAGAGGCGGCAAAGCTGTCCGCCGCCGCCACCCACATCGAGGCCCCGGCCGCGCAGGCTATCCCCAGGGCCCGTGTGCGCAGGGGATCGGTGGGCGGCAGCATTTGGTTGGTGGCGATAAAGTGGAAAAGCCCGTCCGGACTGAAGGTCTCGTGGGCGGCGGCGAACAAGGCACACAGGGCCGTGCCTCCCAAAAACACGGACATCCCCCAAAACACGGGCGCCGACAACGGCAGACGATCCCTCTTGATGTTAACGTACAGGAGGAGCGCCCGCACCGCCCACGTAACGTAGTAGCCGACGATGGCGGCCAGGATACAGGCCGGCGCCACCACCCTTCCGGTCAGCCCGTAATACATGCCCGCTGCCACCATCTCCAACGGCTTCAGGACCAAAAACGACCAAAGGAACAGAATCACGCGCTTTGAAAAGACCGGCTGGGTATGGGGCGGAAGACGCGAGTATGCCGAACTGACAAAAAAGTCAGAGGTGCCGTACGAGGACAATGAAAACTGTTCCTCCAGTGGCAGTTCTCCCTCCTCCCCCCCAAAGGCGGCCTCGTCGACCAGATCTCGATCCACCAGAGGAAGGTCATCCCGCATGGTCATGGGGTGTGCGGTGGAGGTGGGGAGACCGAAACCGCAAAGGGTCGCTTACGTCAGCAGGATCCCGAGATCAAAGACACCCGGGTTCTTGCACAAACACCACCCGGGTTGCATCCGCGGAGGCGAGTGTTTTGATAAGGCCGTTCCGCGCCTTGATATAACCTTTGATGTTGACCACAAAACCCGGAATTTACGCCTACGCCCCAATGCCCACGCAAGATGAGGTAGGTAACCCCCCCCCGTGGGTGTGACGTTGCGTTTAGTTCATTGGAGGCCAAGGGGAAAATGGGGTGGGGAGGAAACGGAAAACCCAGTAGGCCGTGTTGGGAACACGCCCGGGGTTGTCCTCAAAAGGCAGGGTCCATACTACGGAAGCCGTCGTTGTATTCGAGACCTGCCTGTGCGACGCACGTCGGGGTTGCCTGTGTCCGGTTCGGCCCCACCGCGTGCGGCACGCACGAGGACGAGTCCGCGTGCTTTATTGGCGTTCCAAGCGTTGCCCTCCAGTTTCTGTTGTCGGTGTTCCCCCATACCCACGCCCACATCCACCGTAGGGGGCCTCTGGGCCGTGCACGTCGCCGCCCGCGATGGAGCTTAGCTACGCCACCACCATGCACTACCGGGACGTTGTGTTTTACGTCACAACGGACCGAAACCGGGCCTACTTTGTGTGCGGGGGGTGTGTTTATTCCGTGGGGCGGCCGTGTGCCTCGCAGCCCGGGGAGATTGCCAAGTTTGGTCTGGTCGTTCGAGGGACAGGCCCAGACGACCGCGTGGTCGCCAACTATGTACGAAGCGAGCTCCGACAACGCGGCCTGCAGGACGTGCGTCCCATTGGAGGACGAGGTGTTTCTGGACAGCGTGTGTCTTCTAAACCCGAACGTGAGCTCCGAGCTGGATGTGATTAACACGAACGACGTGGAAGTGCTGGACGAATGTCTGGCCGAGTACTGCACCTCGCTGCGAACCAGCCCGGGTGTGCTAATATCCGGGCTGCGCGTGCGGGCGCAGGACAGAATCATCGAGTTGTTTGAACACCCAACGATAGTCAACGTTTCCTCGCACTTTGTGTATACCCCGTCCCCATACGTGTTCGCCCTGGCCCAGGCGCACCTCCCCCGGCTCCCGAGCTCGCTGGAGGCCCTGGTGAGCGGCCTGTTTGACGGCATCCCCGCCCCACGCCAGCCACTTGACGCCCACAACCCGCGCACGGATGTGGTTATCACGGGCCGCCGCGCCCCACGACCCATCGCCGGGTCGGGGGCGGGGTCGGGGGGCGCGGGCGCCAAGCGGGCCACCGTCAGCGAGTTCGTGCAAGTCAAACACATTGACCGCGTGGGCCCCGCTGGCGTTTCGCCGGCGCCTCCGCCAAACAACACCGCTCAAGTTCCCGGTGCCCGGGGCCCAGGATTCCGCCCCGCCCGGCCCCACGCTAAGGGAGCTGTGGTGGGTGTTTTATGCCGCAGACCGGGCGCTGGAGGAGCCCCGCGCCGACTCTGGCCTCACCCGCGAGGAGGTACGTGCCGTACGTGGGTTCCGGGAGCAGGCGTGGAAACTGTTTGGCTCCGCGGGGGCCCCGCGGGCGTTTATCGGGGCCGCGTTGGGCCTGAGCCCCCTCCAAAAGCTAGCCGTTTACTACTATATCATCCACCGAGAGAGGCGCCTGTCCCCCTTCCCCGCGCTAGTCCGGCTCGTAGGCCGGTACACACAGCGCCACGGCCTGTACGTCCCTCGGCCCGCGCTGGAGGCCCTGGTGAGCGGCCTGTTTGACGGCATCCCCGCCCCACGCCAGCCACTTGACGCCCACAACCCGCGCACGGATGTGGTTATCACGGGCCGCCGCGCCCCACGACCCATCGCCGGGTCGGGGGCGGGGTCGGGGGGCGCGGGCGCCAAGCGGGCCACCGTCAGCGAGTTCGTGCAAGTCAAACACATTGACCGCGTGGGCCCCGCTGGCGTTTCGCCGGCGCCTCCGCCAAACAACACCGACTCAAGTTCCCTGGTGCCCGGGGCCCAGGATTCCGCCCCGCCCGGCCCCACGCTAAGGGAGCTGTGGTGGGTGTTTTATGCCGCAGACCGGGCGCTGGAGGAGCCCCGCGCCGACTCTGGCCTCACCCGCGAGGAGGTACGTGCCGTACGTGGGTTCCGGGAGCAGGCGTGGAAACTGTTTGGCTCCGCGGGGGCCCCGCGGGCGTTTATCGGGGCCGCGTTGGGCCTGAGCCCCCTCCAAAAGCTAGCCGTTTACTACTATATCATCCACCGAGAGAGGCGCCTGTCCCCCTTCCCCGCGCTAGTCCGGCTCGTAGGCCGGTACACACAGCGCCACGGCCTGTACGTCCCTCGGCCCGACGACCCAGTCTTGGCCGATGCCATCAACGGGCTGTTTCGCGACGCGCTGGCGGCCGGAACCACAGCCGAGCAGCTCCTCATGTTCGACCTTCTCCCCCCAAAGGACGTGCCGGTGGGAAGCGACGTGCAGGCCGACAGCACCGCTCTGCTGCGCTTTATAGAATCGCAACGTCTCGCCGTCCCCGGGGGGGTGATCTCCCCCGAGCACGTCGCGTACCTTGGTGCGTTCCTGAGCGTGCTGTACGCTGGCCGCGGGCGCATGTCCGCAGCCACGCACACCGCGCGGCTGACAGGGGTGACCTCCCTGGTGCTAGCGGTGGGTGACGTGGACCGTCTTTCCGCGTTTGACCGCGGAGCGGCGGGCGCGGCCAGCCGCACGCGGGCCGCCGGGTACCTGGATGTGCTTCTTACCGTTCGTCTCGCTCGCTCCCAACACGGACAGTCTGTGTAACAGACCCCAATAAACGTATGTCGCTACCACACCCTTGTGTGTCAATGGACGCCTCTCCGGGGGGGAAGGGAAAACAAAGAGGGGCTGGGGGAGCGGCACCACCGGGGCCTGAACAAACAAACCACAGACACGGTTACAGTTTATTCGGTCGGGCGGAGAAACGGCCGAAGCCACGCCCCCTTTATTCGCGTCTCCAAAAAAACGGGACACTTGTCCGGAGAACCTGTAGGATGCCAGCCAGGGCGGCGGTAATCATAACCACGCCCAGCGCAGAGGCGGCCAGAAACCCGGGCGCAATTGCGGCCACGGGCTGCGTGTCAAAGGCTAGCAAATGAATGACGGTTCCGTTTGGAAATAGCAACAAGGCCGTGGACGGCACGTCGCTCGAAAACACGCTTGGGGCGCCCTCCGTCGGCCCGGCGGCGATTTGCTGCTGTGTGTTGTCCGTATCCACCAGCAACACAGACATGACCTCCCCGGCCGGGGTGTAGCGCATAAACACGGCCCCCACGAGCCCCAGGTCGCGCTGGGTTTGGGTGCGCACCAGCCGCTTGGACTCGATATCCCGGGTGGAGCCTTCGCATGTCGCGGGAGGTAGGTTAGGAACAGTGGGCGTCGGACGTCGACGCCGGTGAGCTTGTAGCCGATCCCCCGGGGGAGAGGGGAGGGGGAAGAGAAGAGGGCGTTGTGGGTGATGGGTACCAGGATCCGTGGCTCGACGTTGGCAGACTGCCCCCCGCACCGATGTGAGGCCTCAGGGACGAAGGCGCGGATCAGGGCGTTGTAGTGTGCCCAGCGCGTCAGGGTCGAGGCGAGGCCGTGGGTCTGCTGGGCCAGGACTTCGACCGGGGTCTCGGATCGGGTGGCTTGAGCCAGCGCGTCCAGGATAAACACGCGCTCGTCTAGATCAAAGCGCAGGGAGGCCGCGCATGGCGAAAAGTGGTCCGGAAGCCAAAAGAGGGTTTTCTGGTGGTCGGCCCGGGCCAGCGCGGTCCGGAGGTCGGCGTTGGTCGCTGCGGCGACGTCGGACGTACACAAGGCCGAGGCTATCAGAAGGCTCCGGCGGGCGCGTTCCCGCTGCACCGCCGAGGGGACGCCCGCCAAGAACGGCTGCCGGAGGACAGCCGAGGCGTAAAATAGCGCCCGGTGGACGACCGGGGTGGTCAGCACGCGGCCCCCTAGAAACTCGGCATACAGGGCGTCGATGAGATGGGCTGCGCTGGGCGCCACTGCGTCGTACGCCGAGGGGCTATCCAGCACGAAGGCCAGCTGATAGCCCAGCGCGTGTAATGCCAAGCTCTGTTCGCGCTCCAGAATCTCGGCCACCAGGTGCTGGAGCCGAGCCTCTAGCTGCAGGCGGGCCGTGGGATCCAAGACTGACACATTAAAAAACACAGAATCCGCGGCACAGCCCGCGGCCCCGCGGGCGGCCAACCCGGCAAGCGCGCGCGAGTGGGCCAAAAAGCCTAGCAGGTCGGAGAGGCAGACCGCGCCGTTTGCGTGGGCGGCGTTCACGAAAGCAAAACCCGACGTCGCGAGCAGCCCCGTTAGGCGCCAGAAGAGAGGGGGACGCGGGCCCTGCTCGGCGCCCGCGTCCCCCGAGAAAAACTCCGCGTATGCCCGCGACAGGAACTGGGCGTAGTTCGTGCCCTCCTCCGGGTAGCCGCCCACGCGGCGGAGGGCGTCCAGCGCGGAGCCGTTGTCGGCCCGCGTCAGGGACCCTAGGACAAAGACCCGATACCGGGGGCCGCCCGGGGGCCCGGGAAGAGCCCCCGGGGGGTTTTCGTCCGCGGGGTCCCCGACCCGATCTAGCGTCTGGCCCGCGGGGACCACCATCACTTCCACCGGAGGGCTGTCGTGCATGGATATCACGAGCCCCATGAATTCCCGCCCGTAGCGCGCGCGCACCAGCGCGGCATCGCACCCGAGCACCAGCTCCCCCGTCGTCCAGATGCCCACGGGCCACGTCGAGGCCGACGGGGAGAAATACACGTACCTACCTGGGGATCTCAACAGGCCCCGGGTGGCCAACCAGGTCGTGGACGCGTTGTGCAGGTGCGTGATGTCCAGCTCCGTCGTCGGGTGCCGCCGGGCCCCAACCGGCGGTCGGGGGGGCGGCTGCAGGCGGGCCGTGGGATCCAAGACTGACACATTAAAAAACAGAATCCGCGGCACAGCCCGCGGCCCCGCGGGCGGCCAACCCGGCAAGCGCGCGCGAGTGGGCCAAAAAGCCTAGCAGGTCGGAGAGGCAGACCGCGCCGTTGCGTGGGCGGCGTTCACGAAAGCAAAACCCGACGTCGCGAGCAGCCCCGTTAGGCGCCAGAAGAGAGGGGGACGCGGGCCCTGCTCGGCGCCCGCGTCCCCCGAGAAAAACTCCGCGTATGCCCGCGACAGGAACTGGGCGTAGTTCGTGCCCTCCTCCGGGTAGCCGCCCACGCGGCGGAGGGCGTCCAGCGCGGAGCCGTTGTCGGCCCGCGTCAGGGACCCTAGGACAAAGACCCGATACCGGGGGCCGCCCGGGGGCCCGGGAAGAGCCCCCGGGGGGTTTCGTCCGCGGGGTCCCCGACCCGATCTAGCGTCTGGCCCGCGGGGACCACCATCACTTCCACCGGAGGGCTGTCGTGCATGGATATCACGAGCCCCATGAATTCCCGCCCGTAGCGCGCGCGCACCAGCGCGGCATCGCACCCGAGCACCAGCTCCCCCGTCGTCCAGATGCCCACGGGCCACGTCGAGGCCGACGGGGAGAAATACACGTACCTACCTGGGGATCTCAACAGGCCCCGGGTGGCCAACCAGGTCGTGGACGCGTTGTGCAGGTGCGTGATGTCCAGCTCCGTCGTCGGGTGCCGCCGGGCCCCAACCGGCGGCGGGGGGGCGGTGTATCACGCGGCCCGCTCGGGTGGCTCGCCGTCGCCACGTTGGCTCCCCGCGGGAAAAGAGGGAACGTCAGGGCCTCGGGGTCAGGGACGGCCGAAAACGTTACCCAGGCCCGGGAACGCAGCAACACGGAGGCGGTTGGATTGTGCAAGAGACCCTTAAGGGGGGCGACCGCGGGGGGAGGCTGGGCGGTCGGCTCGACCGTGATGGGGGCGGGCAGGCTCGCGTTCGGGGGCCGGCCGAGCAGGTAGGTCTTCGAGATGTAAAGCAGCTGGCCGGGGTCCCGCGGAAACTCGGCCGTGGTGACCAATACAAAACAAAAGCGCTCCTCGTACCAGCGAAGAAGGGGCAGAGATGCCGTAGTCAGGTTTAGTTCGTCCGGCGGCGCCAGAAATCCGCGCGGTGGTTTTTGGGGGTCGGGGGTGTTTGGCAGCCACAGACGCCCGGTGTTCGTGTCGCGCCAGTACATGCGGTCCATGCCCAGGCCATCCAAAAACCATGGGTCTGTCTGCTCAGTCCAGTCGTGGACCTGACCCCACGCAACGCCCAAAAGAATAACCCCCACGAACCATAAACCATTCCCCATGGGGGACCCCGTCCCTAACCCACGGGGCCCGTGGCTATGGCAGGGCTTGCCGCCCCGACGTTGGCTGCGAGCCCTGGGCCTTCACCCGAACTTGGGGGTTGGGGTGGGGAAAAGGAAGAAACGCGGGCGTATTGGCCCCAATGGGGTCTCGGTGGGGTATCGACAGAGTGCCAGCCCTGGGACCGAACCCCGCGTTTATGAACAAACGACCCAACACCCGTGCGTTTTATTCTGTCTTTTTATTTCCGTCATAGCGCGGGTTCCTTCCGGTATTGTCTCCTTCCGTGTTTCAGTTAGCCTCCCCCATCTCCCGGGCAAACGTGCGCGCCAGGTCGCAGATCGTCGGTATGGAGCCTGGGGTGGTGACGTGGGTCTGGACCATCCCGGAGGTAAGTTGCAGCAGGGCGTCCCGGCAGCCGGCGGGCGATTGGTCGTAATCCAGGATAAAGACGTGCATGGGACGGAGGCGTTTGGCCAAGACGTCCAAGGCCCAGGCAAACACGTTATACAGGTCGCCGTTGGGGGCCAGCAACTCGGGGGCCCGAAACAGGGTAAATAACGTGTCCCCGATATGGGGTCGTGGGCCCGCGTTGCTCTGGGGCTCGGCACCCTGGGGCGGCACGGCCGTCCCCGAAAGCTGTCCCCAATCCTCCCGCCACGACCCGCCGCCCTGCAGATACCGCACCGTATTGGCAAGCAGCCCGTAAACGCGGCGAATCGCGGCCAACATAGCCAGGTCAAGCCGCTCGCCGGGGCGCTGGCGTTTGGCCAGGCGGTCGATGTGTCTGTCCTCCGGAAGGGCCCCCAACACGATGTTTGTGCCGGGCAAGGTCGGCGGGATGAGGGCCACGAACGCCAGCACGGCCTGGGGGGTCATGCTGCCCATAAGGTATCGCGCGGCCGGGTAGCACAGGAGGGCGGCGATGGGATGGCGGTCGAAGATGAGGGTGAGGGCCGGGGGCGGGGCATGTGAGCTCCCAGCCTCCCCCCCGATATGAGGAGCCAGAACGGCGTCGGTCACGGCATAAGGCATGCCCATTGTTATCTGGGCGCTTGTCATTACCACCGCCGCGTCCCCGGCCGATATCTCACCCTGGTCGAGGCGGTGTTGTGTGGTGTAGATGTTCGCGATTGTCTCGGAAGCCCCCAGCACCTGCCAGTAAGTCATCGGCTCGGGTACGTAGACGATATCGTCGCGCGAACCCAGGGCCACCAGCAGTTGCGTGGTGGTGGTTTTCCCCATCCCGTGAGGACCGTCTATATAAACCCGCAGTAGCGTGGGCATTTTCTGCTCCAGGCGGACTTCCGTGGCTTCTTGCTGCCGGCGAGGGCGCAACGCCGTACGTCGGTTGCTATGGCCGCGAGAACGCGCAGCCTGGTCGAACGCAGACGCGTGTTGATGGCAGGGGTACGAAGCCATACGCGCTTCTACAAGGCGCTTGCCAAAGAGGTGCGGGAGTTTCACGCCACCAAGATCTGCGGCACGCTGTTGACGCTGTTAAGCGGGTCGCTGCAGGGTCGCTCGGTGTTCGAGGCCACACGCGTCACCTTAATATGCGAAGTGGACCTGGGACCGCGCCGCCCCGACTGCATCTGCGTGTTCGAATTCGCCAATGACAAGACGCTGGGCGGGGTTTGTGTCATCATAGAACTAAAGACATGCAAATATATTTCTTCCGGGGACACCGCCAACAAACGCGAGCAACGGGCCACGGGGATGAAGCAGCTGCGCCACTCCCTGAAGCTCCTGCAGTCCCTCGCGCCTCCGGGTGACAAGATAGTGTACCTGTGCCCCGTCCTGGTGTTTGTCGCCCAACGGACGCTCCGCGTCAGCCGCGTGACCCGGCTCGTCCCGCAGAAGGTCTCCGGTAATATCACCGCAGTCGTGCGGATGCTCCAGAGCCTGTCCACGTATACGGTCCCCATGGAGCCTAGGACCCAGCGAGCCCGTCGCCGCCGCGGCGGCGCTGCCCGGGGGTCTGCGAGCAGACCGAAAAGGTCACACTCTGGGGCGCGCGACCCGCCCGAGCCAGCGGCCCGCCAGGTACCACCCGCCGACCAAACCCCCGCCTCCACGGAGGGCGGGGGGGTGCTTAAGAGGATCGCGGCGCTCTTCTGCGTGCCCGTGGCCACCAAGACCAAACCCCGAGCTGCCTCCGAATGAGAGTGTTTCGTTCCTTCCCCCTCCCCCCGCGTCAGACAAACCCTAACCACCGCTTAAGCGGCCCCCGCGAGGTCCGAAGACTCATTTGGATCCGGCGGGAGCCACCTGACAACAACCCCTGGGTTTCCCCACACCAGACGCCGGTCCGCTGTGCCATCGCTCCCCTTCATCCCACCCCCATCTTGTCCCCAAATAAAACAAGGTCTGGTAGTTAGGACAACGACCGCAGTTCTCGTGTGTTATTGTCGCTCTCCGCCTCTCGCAGATGGACCCGTATTGCCCATTTGACGCTCTGGACGTCTGGGAACACAGGCGCTTCATAGTCGCCGATTCCCGAAACTTCATCACCCCCGAGTTCCCCCGGGACTTTTGGCTGTCGCCCGTCTTTAACCTCCCCCGGGAGACGGCGGCGGAGCAGGTGGTCGTCCTGCAGGCCCAGCGCCCAGCGGCTGCCGCTGCCCTGGAGAACGCCGCCATGCAGGCGGCCGAGCTCCCCGTCGATATCGAGCGCCGGTTACGCCCGATCGAACGGAACGTGCACGAGATCGCAGGCGCCCTGGAGGCGCTGGAGACGGCGGCGGCCGCCGCCGAAGAGGCGGATGCCGCGCGCGGGGATGAGCCGGCGGGTGGGGGCGACGGGGGGGCGCCCCCGGGCTGGCCGTCGCGGAGATGGAGGGCCAGATCGTGCGCAACGACCCGCCGCTACGATACGACACCAACCTCCCCGTGGATCTGCTACATATGGTGTACGCGGGCCGCGGGGCGACCGGCTCGTCGGGGGTGGTGTTCGGGACCTGGTACCGCACTATCCAGGACCGCACCATCACGGACTTTCCCCTGACCACCCGCAGTGCCGACTTTCGGGACGGCCGGATGTCCAAGACCTTCATGACGGCGCTGGTCCTGTCCCTGCAGTCGTGCGGCCGGCTGTATGTGGGCCAGCGCCACTATTCCGCCTTCGAGTGCGCCGTGTTGTGTCTCTACCTGCTGTACCGAAACACGCACGGGGCCGCCGACGATAGCGACCGCGCTCCGGTCACGTTCGGGGATCTGCTGGGCCGGCTGCCCCGCTACCTGGCGTGCCTGGCCGCGGGATCGGGACCGAGGGCGGCCGGCCACAGTACCGCTACCGCGACGACAAGCTCCCCAAGACGCAGTTCGCGGCCGGCGGGGGCCGCTACGAACACGGAGCGCTGGCGTCGCACATCGTGATCGCCACGCTGATGCACCACGGGGTGCTCCCGGCGGCCCCGGGGGACGCCCCCGGGACGCGAGCACCCACGGTAACCCCGACGGCGTGGCGCACCACGACGACATAAACCGCGCCGCCGCCGCGTTCCTCAGCCGGGGCCACAACCTATTCCTGTGGGAGGACCAGACTCTGCTGCGGGCAACCGCGAACACCATAACGGCCCTGGGCGTTACCCAGCGGCTCCTCGCGAACGGCAACGTGTACGCGGACCGCCTCAACAACCGCCTGCAGCTGGGCATGCTGATCCCCGGAGCCGTCCCTTCGGAGGCCATCGCCCGTGGGGCCTCCGGGTCCGACTCGGGGGCCATCAAGAGCGGAGACAACAATCTGGAGGCGCTATGTGCCAATTACGTGCTTCCGCTGTACCGGGCCGACCCGGCGGTCGAGCTGACCCAGCTGTTTCCCGGCCTGGCCGCCCTGTGTCTTGACGCCCAGGCGGGGCGGCCGGTCGGGTCGACGCGGCGGGTGGTGGATATGTCATCGGGGGCCCGCCAGGCGGCGCTGGTGCGCCTCACCGCCCTGGAACTCATCAACCGCACCCGCACAAACCCCACCCCCGTGGGGGAGGTTATCCACGCCCACGACGCCCTGGCGATCCAATACGAACAGGGGCTTGGCCTGCTGGCGCAGCAGGCACGCATTGGCTTGGGCTCCAACACCAAGCGTTTCTCCGCGTTCAACGTTAGCAGCGACTACGACATGTTGTACTTTTTATGTCTGGGGTTCATTCCACAGTACCTGTCGGCGGTTTAGTGGGTGGTGGGCGAGGGGGGAGGGGGCATTAGGGAGAAAGAACAAGAGCCTCCGTTGGGTTTTCTTTGTGCCTGTCTCAAAAGGTCATCCCCGTAAACGGCGGGCTCCAGTCCCGGCCCGGCGGTTGGCGTGAACGCAACGGCGGGGCTGGGTTAGCGTTTAGTTTAGCATTCGCTCTCGCCTTTCCGCCCGCCCCCGACCGTTGAGCCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCGTCCACCAAAGTCTCTGTGGGTGCGCGCATGGCAGCCGATGCCCCGGGAGACCGGATGGAGGAGCCCCTGCCAGACAGGGCCGTGCCCATTTACGTGGCTGGGTTTTTGGCCCTGTATGACAGCGGGGACTCGGGCGAGTTGGCATTGGATCCGGATACGGTGCGGGCGGCCCTGCCTCCGGATAACCCACTCCCGATTAACGTGGACCACCGCGCTGGCTGCGAGGTGGGGCGGGTGCTGGCCGTGGTCGACGACCCCCGCGGGCCGTTTTTTGTGGGACTGATCGCCTGCGTGCAACTGGAGCGCGTCCTCGAGACGGCCGCCAGCGCTGCGATTTTCGAGCGCCGCGGGCCGCCGCTCTCCCGGGAGGAGCGCCTGTTGTACCTGATCACCAACTACCTGCCCTCGGTCTCCCTGGCCACAAAACGCCTGGGGGGCGAGGCGCACCCCGATCGCACGCTGTTCGCGCACGTAGCGCTGTGCGCGATCGGGCGGCGCCTTGGCACTATCGTCACCTACGACACCGGTCTCGACGCCGCCATCGCGCCCTTTCGCCCCTGTCGCCGGCGTCTCGCGAGGGGGCGCGGCGACTGGCCGCCGAGGCCGAGCTCGCGCTATCCGGACGCCCCTGGGCGCCCGGCGTGGAGGCGCTGCCCCACACGCTGCTTTCCACCGCCGTTAACAACATGATGCTGCGGGACCGCTGGAGCCTGGTGGCCGAGCGGCGGCGGCAGGCCGGGATCGCCGGACACACCTACCTCCAGGCGAGCGAAAAATTCAAAATGTGGGGGGCGGAGCCTGTTTCCGCGCCGGCGCGCGGGTATAAGAACGGGGCCCCGGAGTCCACGGACAACCGCCCGGCTCGATCGCTGCCGCGCCGCAGGGTGACCGGTGCCCAATCGTCCGTCAGCGCGGGGTCGCCTCGCCCCCGGTACTGCCCCCCATGAACCCCGTTCCAACATCGGGCACCCCGGCCCCCGCGCCGCCCGGCGACGGGAGCTACCTGTGGATCCCGGCCTCCCATACAACCAGCTCGTCGCCGGCCACGCCGCGCCCCAACCCCAGCCGCATTCCGCGTTTGGTTCCCGGCTGCGGCGGGGGCCGTGGCCTATGGGCCTCACGGCGCGGGTCTTTCCCAGCATTACCCTCCCCACGTCGCCCATCAGTATCCCGGGGTGCTGTTCTCGGGACCCAGCCCACTCGAGGCGCAGATAGCCGCGTTGGTGGGGGCCATAGCCGCGGACCGCCAAGCGGGCGGTCAGCCGGCCGCGGGAGACCCTGGGGTCCGGGGGTCGGGAACTCCCTTCCTCTTCCTTTGCCTCGGAGTCCTACTGCCCCACCGACGAACCGGACGCGGACTACCCGTACTACCCCGGGGAGGCTCGAGGCGGGCCGCGCGGGGGCGACTCTCGGCGCGCGGCCCGCCAGTCTCCCGGGACCAACGAGACCATCACGGCGCTGATGGGGGCGGGACGTCTCTGCAGCAGGAACTGGCGCACATGCGGGCTCGGACCAGCGCCCCCTATGGAATGTACACGCCGGTGGCGCACTATCGCCCTCAGGTGGGGGAGCCGGAACCAACAACGACCCACCCGGCCCTTTGTCCCCCGGAGGCCGTGTATCGCCCCCCCCCACACAGCGCCCCCTACGGTCCTCCCCAGGGTCCGGCGTCCCATGCCCCCACTCCCCCGTATGCCCCAGCTGCCTGCCCGCCAGGCCCGCCACCGCCCCCATGTCCTTCCACCCAGACGCGCGCCCCTCTACCGACGGAGCCCGCGTTCCCCCCCGCCGCCACCGGATCCCAACCGGAGGCATCCAACGCGGAGGCCGGGGCCCTTGTCAACGCCAGCAGCGCAGCACACGTGGACGTTGACACGGCCCGCGCCGCCGATTTGTTCGTCTCTCAGATGATGGGGGCCCGCTGATTCGCCCCGGTCTTTGGTACCATGGGATGTCTTACTGTATATCTTTTTAAATAAACCAGGTAATACCAAATAAGACCCATTGGTGTATGTTCTTTTTTTTTTATTGGGAGGGGCGGGTAGGCGGGTAGCTTTACAATGCAAAAGCCTTTGACGTGGAGGAAGGCGTGGGGGGGAGGAAATCGGCACTGACCAAGGGGGTCCGTTTTGTCACGGGAAAGGAAAGAGGAAACAGGCCGCGGACACCCGGGGGAGTTTATGTGTTCCTTTTTCTTTCTTCCCACACACACACAAAAGGCGTACCAAACAAAAAAACCAAAAGATGCGCATGCGGTTTAACACCCGTGGTTTTTATTTACAACAAACCCCCCGTCACAGGTCGTCCTCGTCGGCGTCACCGTCTTTGTTGGGAACTTGGGTGTAGTTGGTGTTGCGGCGCTTGCGCATGACCATGTCGGTGACCTTGGCGCTGAGCAGCGCGCTCGTGCCCTTCTTCTTGGCCTTGTGTTCCGTGCGCTCCATGGCCGACACCAGGGCCATGTACCGTATCATCTCCCTGGCCTCGGCTAGCTTGGCCTCGTCAAAGTCGCCGCCCTCCTCGCCCTCCCCGGACGCGTCCGGGTTGGTGGGGTTCTTGAGCTCCTTGGTGGTTAGAGGGTACAGGGCCTTCATGGGGTTGCTCTGCAGCCGCATGACGTAACGAAAGGCGAAGAAGGCCGCCGCCAGGCCGGCCAGGCCAACAGCCCACGGCCAGCGCCCCAAAGGGGTTGGACATGAAGGAGGACACGCCCGACACGGCCGATACCACGCCGCCCACGATGCCCATCACCACCTTGCCGACCGCGCGCCCCAGGTCGCCCATCCCCTCGAAGAACGCGCCCAGGCCCGCGAACATGGCGGCGTTGGCGTCGGCGTGGATGACCGTGTCGATGTCGGCGAAGCGCAGGTCGTGCAGCTGGTTGCGGCGCTGGACCTCCGTGTAGTCCAGCAGGCCGCTGTCCTTGATCTCGTGGCGGGTGTACACCTCCAGGGGGACAAACTCGTGATCCTCCAGCATGGGGATGTTGAGGTCGATGAAGGGCTGACGGTGGTGATGTCGGCGCGGCTCAGCTGGTGGGAGTACGCGTACTCCTCGAAGTACACGTAGCCCCCACCGAAGGTGAAGTAGCGCCGGTGTCCCACGGTGCACGGCTCGATCGCATCGCGCGTCAGCCGCAGCTCGTTGTTCTCCCCCAGCTGCCCCTCGACCAACGGGCCCTGGTCTTCGTACCGAAAGCTGACCAGGGGGCGGCTGTAGCAGGCCCCGGGCCGCGAGCTGATGCGCATCGAGTTTTGGACGATCACGTTGTCCGCGGCGACCGGCCCGCACGTGGAGACGGCCATCACGTCGCCGAGCATCCGCGCGCTCACCCGCCGGCCCACGGTGACCGAGGCGATGGCGTTGGGGTTCAGCTTGCGGGCCTCGTTCCACAGGGTCAGCTCGTGATTCTGTAGCTCGCACCACGCGATGGCAACGCGGCCCAACATATCGTTGACATGGCGCTGTATGTGGTTGTACGTAAACTGCAGCCGGGCGAACTCGATGGAGGAGGTGGTCTTGATGCGCTCCACGGACGCGTTGGCGCTGGCCCCGGGCGGCGGGGGCGTGGGGTTTGGGGGCTTGCGGCTCTGCTCTCGGAGGTGTCCCGCACGTACAGCTCCGCGAGCGTGTTGCTGAGAAGGGGCTGGTACGCGATCAGAAAGCCCCCATTGGCCAGGTAGTACTGCGGCTGGCCCACCTTGATGTGCGTCGCGTTGTACCTGCGGGCGAAGATGCGGTCCATGGCGTCGCGGGCGTCCTTGCCGATGCAGTCCCCCAGGTCCACGCGCGAGAGCGGGTACTCGGTCAGGTTGGTGGTGAAGGTGGTGGATATGGCGTCGGAGGAGAATCGGAAGGAGCCGCCGTACTCGGAGCGCAGCATCTCGTCCACTTCCTGCCACTTGGTCATGGTGCAGACCGACGGGCGCTTTGGCACCCAGTCCCAGGCCACGGTGAACTTGGGGGTCGTGAGCAGGTTCCGGGTGGTCGGCGCCGGGCCCGGGCCTTGGTGGTGAGGTCGCGCGCGTAGAAGCCGTCGACCTGCTTGAAGCGGTCGGCGGCGTAGCTGGTGTGTTCGGTGTGCGACCCCTCCCGGTAGCCGTAAAACGGGGACATGTACACAAAGTCGCCAGTCGCCAGCACAAACTCGTCGTACGGGTACACCGAGCGCGCGTCCACCTCCTCGACGATGCAGTTTACCGTCGTCCCGTACCGGTGGAACGCCTCCACCCGCGAGGGGTTGTACTTGAGGTCGGTGGTGTGCCAGCCCCGGCTCGTGCGGGTCGCGGCGTTGGCCGGTTTCAGCTCCATGTCGGTCTCGTGGTCGTCCCGGTGAAACGCGGTGGTCTCCAGGTTGTTGCGCACGTACTTGGCCGTGGACCGACAGACCCCCTTGGCGTGATCTTGTCGATCACCTCCTCGAAGGGGACGGGGGCGCGGTCCTCAAAGATCCCCATAAACTGGGAGTAGCGGTGGCCGAACCACACCTGCGAAACGGTGACGTCTTTGTAGTACATGGTGGCCTTGAACTTGTACGGGGCGATGTTCTCCTTGAAGACCACCGCGATGCCCTCCGTGTAGTTCTGACCCTCGGGCCGGGTCGGGCAGCGGCGCGGCTGCTCGAACTGCACCACCGTGGCGCCCGTGGGGGGTGGGCACACGTAAAAGTTTGCATCGGTGTTCTCCGCCTTGATGTCCCGCAGGTGCTCGCGCAGGGTGGCGTGGCCCGCGGCGACGGTCGCGTTGTCGCCGGCGGGGCGTGGGGGCGTTGGGTTTTTCGGTTTTTTGTTCTTCTTCGGTTTCGGGTCCCCCGTTGGGGCGGCGCCAAGGGCGGGCGGCGCCGGAGTGGCAGGGCCCCCGTTCGCCGCCTGGGTCGCGGCCGCGACCCCAGGCGTGCCGGGGGAACTCGGAGCCGCCGACGCCACCAGGACCCCCAGCGTCAACCCCAAGAGCGCCCATACGACGAACCACCGGCGCCCCCACGAGGGGGCGCCCTGGTGCATGGCGGGACTACGGGGGCCCGTCGTGCCCCCCGTCAGGTAGCCTGGGGGCGAGGTGCTGGAGGACCGAGTAGAGGATCGAGAAAACGTCGCGGTCGTAGACCACGACGACCGGGGGCCGATACAGCCGTCGGGGGCGCTCTCGACGATGGCCACCAGCGGACAGTCGGAGTCGTACGTGAGATATACGCCGGGCGGGTAACGGTAACGACCTTCGGAGGTCGGGCGGCTGCAGTCCGGGCGGGCAACTCGAGCTCCCCGCACCGGTAGACCGAGGCAAAGAGTGTGGTGGCGATAATCAGCTCGCGAATATATCGCCAGGCGGCGCGCTGAGTGGGCGTTATTCCGGAAATGCCGTCAAAACAGTAAAACCTCTGAAATTCGCTGACGGCCCAATCAGCACCCGAGCCCCCCGCCCCCATGATGAACCGGGCGAGCTCCTCCTTCAGGTGCGGCAGGAGCCCCACGTTCTCGACGCTGTAATACAGCGCGGTGTTGGGGGGCTGGGCGAAGCTGTGGGTGGAGTGATCAAAGAGGGGCCCGTTGACGAGCTCGAAGAAGCGATGGGTGATGCTGGGGAGCAGGGCCGGGTCCACCTGGTGTCGCAGGAGAGACGCTCGCATGAACCGGTGCGCGTCGAACACGCCCGGCGCCGAGGGTTGTCGATGACCGTGCCCGCGCCCGCCGTCAGGGCGCAGAAGCGCGCGCGCGCCGCAAAGCCGTTGGCGACCGCGGCGAACGTCGCGGGCAGCACCTCGCCGTGGACGCTGACCCGCAGCATCTTCTCGAGCTCCCCGCGCTGCTCGCGGACGCAGCGCCCCAGGCTGGCCAACGACCGCTTCGTCAGGCGGTCCGCGTACAGCCGCCGTCGCTCCCGTACGTCCGCGGCCGCTTGCGTGGCGATGTCCCCCCACGTCTCGGGCCCCTGCCCCCCGGGCCCGCGGCGACGGTCTTCGTCCTCGCCCCCGCCCCCAGGAGCTCCCAACCCCCGTGCCCCTTCCTCTACGGCGACACGGTCCCCGTCGTCGTCGGGGCCCGCGCCGCCCTTGGGCGCGTCCGCCGCGCCCCCCGCCCCCATGCGCGCCAGCACGCGACGCAGCGCCTCCTCGTCGCACTGTTCGGGGCTGACGAGGCGCCGCAAGAGCGGCGTCGTCAGGTGGTGGTCGTAGCACGCGCGGATGAGCGCCTCGATCTGATCGTCGGGTGACGTGGCCTGACCGCCGATTATTAGGGCGTCCACCATATCCAGCGCCGCCAGGTGGCTCCCGAACGCGCGATCGAAATGCTCCGCCCGCCGCCCGAACAGCGCCAGTTCCACGGCCACCGCGGCGGTCTCCTGCTGCAACTCGCGCCGCGCCAGCGCGGTCAGGTTGCTGGCAAACGCGTCCATGGTGGTCTGGCCGGCGCGGTCGCCGGACGCGAGCCAGAATCGCAATTCGCTGATGGCGTACAGGCCGGGCGTGGTGGCCTGAAACACGTCGTGCGCCTCCAGCAGGGCGTCGGCCTCCTTGCGGACCGAGTCGTTCTCGGGCGACGGGTGGGGCTGCCCGTCGCCCCCCGCGGTCCGGGCCAGCGCATGGTCCAACACGGAGAGCGCCCGCGCGCGGTCGGCGTCCGACAGCCCGGCGGCGTGGGGCAGGTACCGCCGCAGCTCGTTGGCGTCCAGCCGCACCTGCGCCTGCTGGGTGACGTGGTTACAGATACGGTCCGCCAGGCGGCGGGCGATCGTCGCCCCCTGGTTCGCCGTCACACACAGTTCCTCGAAACAGACCGCGCAGGGGTGGGACGGGTCGCTAAGCTCCGGGGGGACGATAAGGCCCGACCCCACCGCCCCCACCATAAACTCCCGAACGCGCTCCAGCGCGGCGGGGGGCAGGTACCGCCGCAGCTCGTTGGCGTCCAGCCGCACCTGCGCCTGCTGGGTGACGTGGTTACAGATACGGTCCGCCAGGCGGCGGGCGATCGTCGCCCCCTGGTTCGCCGTCACACACAGTTCCTCGAAACAGACCGCGCAGGGGTGGGACGGGTCGCTAAGCTCCGGGGGGACGATAAGGCCCGACCCCACCGCCCCCACCATAAACTCCCGAACGCGCTCCAGCGCGGCGGTGGCGCCGCGCGAGGGGGTGATGAGGGGCAGTAGTTTAGCTGCTTTAGAAAGTTCTCGACGTCGTGCAGGAAACACAGCTCCATATGGACGGTCCCGCCATACGTATCCAGCCTGACCCGTTGGTGATACGGACAGGGTCGGGCCAGGCCCATGGTCTCGGTGAAAAACGCCGCGACGTCTCCCGCGTACGCGAACGTCTCCAGGTTGCCCAGGAGCCGCTCGCCCTCGCGCCACGCGTACTCTAGCAGCAACTCCAGGGTGACCGACAGCGGGGTGAGAAAGGCCCCGGCCTGGGCCTCCAGGCCCGGCCTCAGACGACGCCGCAGCGCCCGCACCTGAAGCGCGTTCAGCTTCAGTTGGGGGAGCTTCCCCCGTCCGATGTGGGGGTCGCACCGCCGGAGCAGCTCTATCTGAAACACATAGGTCTGCACCTGCCCGAGCAGGGCTAACAACTTTTGACGGGCCACGGTGGGCTCGGACACCGGGGCGGCCATCTCGCGGCGCCGATCTGTACCGCGGCCGGAGTATGCGGTGGACCGAGGCGGTCCGTACGCTACCCGGTGTCTGGCTGAGCCCCGGGGTCCCCCTCTTCGGGGCGGCCTCCCGCGGGCCCGCCGACCGGCAAGCCGGGAGTCGGCGGCGCGTGCGTTTCTGTTCTATTCCCAGACACCGCGGAGAGGAATCACGGCCCGCCCAGAGATATAGACACGGAACACAAACAAGCACGGATGTCGTAGCAATAATTTATTTTACACACATTCCCCGCCCCGCCCTAGGTTCCCCCACCCCCCAACCCCTCACAGCATATCCAACGTCAGGTTTCCCTTTTTGTCGGGGGGCCCCTCCCCAAACGGGTCATCCCCGTGGAACGCCCGTTTGCGGCCGGCAAATGCCGGTCCCGGGGCCCCCGGGCCGCCGAACGGCGTCGCGTTGTCGTCCTCGCAGCCAAAATCCCCAAAGTTAAACCCCTCCCCGGCGTTGCCGAGTTGGCTGACTAGGGCCTCGGCCTCGTGCGCCACCTCCAGGGCCGCGTCCGTCGACCACTCGCCGTTGCCGCGCTCCAGGGCACGCGCGGTCAGCTCCATCATCTCCTCGCTTAGGTACTCGTCCTCCAGGAGCGCCAGCCAGTCCTCGATCTGCAGCTGCTGGGTGCGGGGCCCCAGGCTTTTCACGGTCGCCACGAACACGCTACTGGCGACGGCCGCCCCGCCCTCGGAGATAATGCCCCGGAGCTGCTCGCACAGCGAGCTTTCGTGCGCTCCGCCGCCGAGGTTCGAGGCCGCGCACACAAACCCGGCCCGGGGACAGGCCAGGACGAACTTGCGGGTGCGGTCAAAAATAAGGAGAGGGAGGTTTTTGCCGCCCATCAGGCTGGCCCAGTTCCCGGCCTGAAACACACGGTCGTTGCCGGCCATGCCGTAGTATTTGCTGTTGCACAACCCCAACACGACACTGGGGCGCGCCGCCATGACGGGCCGCAGCAGGTTGCAGCTGGCGAACATGGACGTCCACGCGCCCGGATGCGCGTCCACGGCGTCCATCAGCGCGCGGGCCCCGGCCTCCAGGCCCGCCCCGCCCTGCGCGGACCACGCGGCCGCCGCCTGCACGCTGGGGGGACGGCGGGACCCCGCGATGATGGCCGTGAGGGTGTTGATGAAGTATGTCGAGTGATCGCAGTACCGCAGAATCTGGTTTGCCATGTAGTACATCGCCAGCTCGCTCACGTTGTTGGGGGCCAGGTAATAAAGTTTATCGCGCCGTAGTCCAGGGAAAACTTTTTAATGAACGCGATGGTCTCGATGTCCTCGCGCGACAGGAGCCGGGCGGGAAGCTGGTTGCGTTGGAGGGCCGTCCAGAACCACTGCGGGTTCGGCTGGTTGGACCCCGGGGGCTTGCCGTTGGGGAAGATGGCCGCGTGGAACTGCTTCAGCAGAAAGCCCAGCGGTCCGAGGAGGATGTCCACGCGCTTGTCGGGCTGCTGGGGGGGGGTGGGGAGGCTGGCGACCCGCGCCTTGGCGGCCTCGGACGCGTTGGCGCTCGCGCCCGCGAACAACACGCGGCTCTTGACGCGCAGCTCCTTGGGAAACCCCAGGGTCACGCGGGCAACGTCGCCCTCGAAGCTGCTCTCGGCGGGGGCCGTCTGGCCGGCCGTTAGGCTGGGGGCGCAGATAGCCGCCCCCTCCGAGAGCGCGACCGTCAGCGTTTTGGCCGACAGAAACCCGTTGTTAAACATGTCCATCACGCGCCGCCGCAGCACCGGTTGGAATTGATTGCGAAAGTTGCGCCCCTCGACCGACTGCCCGGCGAACACCCCGTGGCACTGGCTCAGGGCCAGGTCCTGATACACGGCGAGGTTGGATCGCCGCCCGAGAAGCTGAAGCAGGGGGCATGGCCCGCACGCGTACGGGTCCAGCGTCAGGGACATGGCGTGGTTGGCCTCGCCCAGACCGTCGCGAAACTTGAAGTTCCTCCCCTCCCCAGGTTGCGCATCAGCTGCTCCACCTCGCGGTCCACGACCTGCCTGACGTTGTTCACCACCGTATGCAGGGCCTCGCGGTTGGTGATGATGGTCTCCAGCCGCCCCATGGCCGTGGGGACCGCCTGGTCCACGTACTGCAGGGTCTCGAGTTCGGCCATGACGCGCTCGGTCGCCGCGCGGTACGTCTCCTGCATGATGGTCCGGGCGGTCTCGGATCCGTCCGCGCGCTTCAGGGCCGAGAAGGCGGCGTAGTTTCCCAGCACGTCGCAGTCGCTGTACATGCTGTTCATGGTCCCGAAGACGCCGATGGCTCCGCGGGCGGCGCTGGCGAACTTGGGATGGCGCGCCCGGAGGCGCATGAGCGTCGTGTGTACGCAGGCGTGGCGCGTGTCGAAGGTGCACAGGTTGCAGGGCACGTCGGTCTGGTTGGAGTCCGCGACGTATCGAAACACGTCCATCTCCTGGCGCCCGACGATCACGCCGCCGTCGCAGCGCTCCAGGTAAAACAGCATCTTGGCCAGCAGCGCCGGGGAAAACCCACACAGCATGGCCAGGTGCTCGCCGGCAAATTCCTGGGTTCCGCCGACGAGGGGCGCGGTGGGCCGACCCTCGAACCCGGGCACCACGTGTCCCTCGCGGTCCACCTGTGGGTTGGCCGCCACGTGGGTCCCGGGCACGAGGAAGAAGCGGTAAAAGGAGGGTTTGCTGTGGTCCTTTGGGTCCGCCGGACCGGCGTCGTCCACCTCGGTGAGATGGAGGGCCGAGTTGGTGCTAAATACCATGGCCCCCACGAGTCCCGCGGCGCGCGCCAGGTACGCCCCGACGGCGTTGGCGCGGGCCGCGGCCGTGTCCTGGCCCTCGCACAGCGGCCACGCGGAGATGTCGGTGGGCGGCTCGTCGAAGACGGCCATCGACACGATAGACTCGAGGGCCAGGGCGGCGTCTCCGGCCATGACGGAGGCCAGGCGCTGTTCGAACCCGCCCGCCGGGCCCTTGCCGCCGCCGTCGCGCCCACCCCGCGGGGTCTTACCCTGGCTGGCTTCGAAGGCCGTGAACGTAATGTCGGCGGGGAGGGCGGCGCCCTCGTGGTTTTCGTCAAACGCCAGGTGGGCGGCCGCGCGGGCCACGGCGTCCACGTTTCGGCATCGCAGTGCCACGGCGGCGGGTCCCACGACCGCCTCGAACAGGAGGCGGTTGAGGGGGCGGTTAAAAAACGGAAGCGGGTAGGTAAAATTCTCCCCGATCGATCGGTGGTTGGCGTTGAACGGCTCGGCGATGACCCGGCTAAAATCCGGCATGAACAGCTGCAACGGATACACGGGTATGCGGTGCACCTCCGCCCCGCCTATGGTTACCTTGTCCGAGCCTCCCAGGTGCAGAAAGGTGTTGTTGATGCACACGGCCTCCTTGAAGCCCTCGGTAACGACCAGATACAGGAGGGCGCGGTCCGGGTCCAGGCCGAGGCGCTCACACAGCGCCTCCCCCGTCGTCTCGTGTTTGAGGTCGCCGGGCCGGGGGGTGTAGTCCGAAAAGCCAAAATGGCGGCGTGCCCGCTCGCAGAGTCGCGTCAGGTTTGGGGCCTGGGTGCTGGGGTCCAGGTGCCGGCCGCCGTGAAAGACGTACACGGACGAGCTGTAGTGCGATGGCGTCAGTTTCAGGGACACCGCGGTACCCCCGAGCCCCGTCGTGCGAGAACCCACGACCACGGCTACGTTGGCCTCAAAGCCGCTCTCCACGGTCAGGCCCACGACCAGGGGCGCCACGGCGACGTCGGCATCGCCGCTGCGCGCCGACAGTAACGCCAGAAGCTCGATGCCTTCGGACGGACACGCGCGAGCGTACACGTATCCCAGGGGCCCGGGGGGGACCTTGATGGTGGTTGCCGTCTTGGGCTTTGTCTCCATGTCCTCCTGGCAATCGGTCCGCAAACGGAGGTAATCCCGGCACGACGACGGACGCCCGACGAGGTATGTCTCCCGAGCGTCAAAATCCGGGGGGGGGGCGGCGACGGTCAAGGGGAGGGTGGGAGACCGGGGTTGGGGAATGAATCCCTACCCTTCACAGACAACCCCCGGGTAACCACGGGGTGCCGATGAACCCCGGCGGCTGGCAACGCGGGGTCCCTGCGAGAGGCACAGATGCTTACGGTCAGGTGCTCCGGGCCGGGTGCGTCTGATATGCGGTTGGTATATGTACACTTTACCTGGGGGCGTGCCGGACCGCCCCAGCCCCTCCCACACCCCGCGCGTCATCAGCCGGTGGGCGTGGCCGCTATTATAAAAAAAGTGAGAACGCGAAGCGTTCGCACTTTGTCCTAATAATATATATATTATTAGGACAAAGTGCGAACGCTTCGCGTTCTCACTTTTTTTATAATAGCGGCCACGCCCACCGGCTACGTCACGCTCCTGTCGGCCGCCGGCGGTCCATAAGCCCGGCCGGCCGGGCCGACGCGAATAAACCGGGCCGCCGGCCGGGGCGCCGCGCAGCAGCTCGCCGCCCGGATCCGCCAGACAAACAAGGCCCTTGCACATGCCGGCCCGGGCGAGCCTGGGGGTCCGGTAATTTTGCCACCCCCCCAGCGGCTTTTGGGGTTTTTCCTCTTCCCCCCTCCCCACATCCCCCCCCTTTAGGGGTTCGGGTGGGACAACCGCGATGTTTTCCGGTGGCGGCGGCCCGCTGTCCCCCGGAGGAAAGTCGGCGGCCAGGGCGGCGTCCGGGTTTTTTGCGCCCGCCGGCCCTCGCGGAGCCGGCCGGGGACCCCCGCCTTGTTTGAGGCAAAACTTTTACAACCCCTACCTCGCCCCAGTCGGGACGCAACAGAAGCCGACCGGGCCAACCCAGCGCCATACGTACTATAGCGAATGCGATGAATTTCGATTCATCGCCCCGCGGGTGCTGGACGAGGATGCCCCCCCGGAGAAGCGCGCCGGGGTGCACGACGGTCACCTCAAGCGCGCCCCCAAGGTGTACTGCGGGGGGGACGAGCGCGACGTCCTCCGCGTCGGGTCGGGCGGCTTCTGGCCGCGGCGCTCGCGCCTGTGGGGCGGCGTGGACCACGCCCCGGCGGGGTTCAACCCCACCGTCACCGTCTTTCACGTGTACGACATCCTGGAGAACGTGGAGCACGCGTACGGCATGCGCGCGGCCCAGTTCCACGCGCGGTTTATGGACGCCATCACACCGACGGGGACCGTCATCACGCCCCTGGGCCTGACTCCGGAAGGCCACCGGGTGGCCGTTCACGTTTACGGCACGCGGCAGTACTTTTACATGAACAAGGAGGAGGTTGACAGGCACCTACAATGCCGCGCCCCACGAGATCTCTGCGAGCGCATGGCCGCGGCCCTGCGCGAGTCCCCGGGCGCGTCGTTCCGCGGCATCTCCGCGGACCACTTCGAGGCGGAGGTGGTGGAGCGCACCGACGTGTACTACTACGAGACGCGCCCCGCTCTGTTTTACCGCGTCTACGTCCGAAGCGGGCGCGTGCTGTCGTACCTGTGCGACAACTTCTGCCCGGCCATCAAGAAGTACGAGGGTGGGGTCGACGCCACCACCCGGTTCATCCTGGACAACCCCGGGTTCGTCACCTTCGGCTGGTACCGTCTCAAACCGGGCCGGAACAACACGCTAGCCCAGCCGCGGGCCCCGATGGCCTTCGGGACATCCAGCGACGTCGAGTTTAACTGTACGGCGGACAACCTGGCCATCGAGGGGGGCATGAGCGACCTACCGGCATACAAGCTCATGTGCTTCGATATCGAATGCAAGGCGGGGGGGGAGGACGAGCTGGCCTTTCCGGTGGCCGGGCACCCGGATGACCTGGTTATTCAGATATCCTGTCTGCTCTACGACCTGTCCACCACCGCCCTGGAGCACGTCCTCCTGTTTTCGCTCGGTTCCTGCGACCTCCCCGAATCCCACCTGAACGAGCTGGCGGCCAGGGGCCTGCCCACGCCCGTGGTTCTGGAATTCGACAGCGAATTCGAGATGCTGTTGGCCTTCATGACCCTTGTGAAACAGTACGGCCCCGAGTTCGTGACCGGGTACAACATCATCAACTTCGACTGGCCCTTCTTGCTGGCCAAGCTGACGGACATTTACAAGGTCCCCCTGGACGGGTACGGCCGCATGAACGGCCGGGGCGTGTTTCGCGTGTGGGACATAGGCCAGAGCCACTTCCAGAAGCGCAGCAAGATAAAGGTGAACGGCATGGTGAACATCGACATGTACGGGATCATAACCGACAAGATCAAGCTCTCGAGCTACAAGCTCAACGCCGTGGCCGAAGCCGTCCTGAAGGACAAGAAGAAGGACCTGAGCTATCGCGACATCCCCGCCTACTACGCCACCGGGCCCGCGCAACGCGGGGTGATCGGCGAGTACTGCATACAGGATTCCCTGCTGGTGGGCCAGCTGTTTTTTAAGTTTTTGCCCCATCTGGAGCTCTCGGCCGTCGCGCGCTTGGCGGGTATTAACATCACCCGCACCATCTACGACGGCCAGCAGATCCGCGTCTTTACGTGCCTGCTGCGCCTGGCCGACCAGAAGGGCTTTATTCTGCCGGACACCAGGGGCGATTTAGGGGCGCCGGGGGGGAGGCGCCCAAGCGTCCGGCCGCAGCCCGGGAGGACGAGGAGCGGCCAGAGGAGGAGGGGGAGGACGAGGACGAACGCGAGGAGGGCGGGGGCGAGCGGGAGCCGGAGGGCGCGCGGGAGACCGCCGGCCGGCACGTGGGGTACCAGGGGGCCAGGGTCCTTGACCCCACTTCCGGGTTTCACGTGAACCCCGTGGTGGTGTTCGACTTTGCCAGCCTGTACCCCAGCATCATCCAGGCCCACAACCTGTGCTTCAGCACGCTCTCCCTGAGGGCCGACGCAGTGGCGCACCTGGAGGCGGGCAAGGACTACCTGGAGATCGAGGTGGGGGGGCGACGGCTGTTCTTCGTCAAGGCTCACGTGCGAGAGAGCCTCCTCAGCATCCTCCTGCGGGACTGGCTCGCCATGCGAAAGCAGATCCGCTCGCGGATTCCCCAGAGCAGCCCCGAGGAGGCCGTGCTCCTGGACAAGCAGCAGGCCGCCATCAAGGTCGTGTGTAACTCGGTGTACGGGTTCACGGGAGTGCAGCACGGACTCCTGCCGTGCCTGCACGTTGCCGCGACGGGACGACCATCGGCCTGGAGATCGAGGTGGGGGGGCGACGGCTGTTCTTCGTCAAGGCTCACGTGCGAGAGAGCCTCCTCAGCATCCTCCTGCGGGACTGGCTCGCCATGCGAAAGCAGATCCGCTCGCGGATTCCCCAGAGCAGCCCCGAGGAGGCCGTGCTCCTGGACAAGCAGCAGGCCGCCATCAAGGTCGTGTGTAACTCGGTGTACGGGTTCACGGGAGTGCAGCACGGACTCCTGCCGTGCCTGCACGTTGCCGCGACGGTGACGACCATCGGCCGCGAGATGCTGCTCGCGACCCGCGAGTACGTCCACGCGCGCTGGGCGGCCTTCGAACAGCTCCTGGCCGATTTCCCGGAGGCGGCCGACATGCGCGCCCCCGGGCCCTATTCCATGCGCATCATCTACGGGGACACGGACTCCATATTTGTGCTGTGCCGCGGCCTCACGGCCGCCGGGCTGACGGCCATGGGCGACAAGATGGCGAGCCACATCTCGCGCGCGCTGTTTCTGCCCCCCATCAAACTCGAGTGCGAAAAGACGTTCACCAAGCTGCTGCTGATCGCCAAGAAAAAGTACATCGGCGTCATCTACGGGGGTAAGATGCTCATCAAGGGCGTGGATCTGGTGCGCAAAAACAACTGCGCGTTTATCAACCGCACCTCCAGGGCCCTGGTCGACCTGCTGTTTTACGACGATACCGTTCCGGAGCGGCCGCCGCGTTAGCCGAGCGCCCCGCAGAGGAGTGGCTGGCGCGCCCCTGCCCGAGGGACTGCAGGCGTTCGGGGCCGTCCTCGTAGACGCCCATCGGCGCATCACCGACCCGGAGAGGGACATCCAGGACTTTGTCCTCACCGCCGAACTGAGCAGACACCCGCGCGCGTACACCAACAAGCGCCTGGCCCACCTGACGGTGTATCAGCTCATGGCCCGCCGCGCGCAGGTCCCGTCCATCAAGGACCGGATCCCGTCGTGTCGGGCCCGCCCGCGAGGAGGGAGACGGTCGCGCGGCTGGCCGCCCTCCGCGAGCTAGACGCCGCCGCCCCAGGGGACGAGCCCGCCCCCCCCGCGGCCCTGCCCTCCCCGGCCAAGCGCCCCCGGGAGACGCCGTCGCATGCCGACCCCCCGGGAGGCGCGTCCAAGCCCCGCAAGCTGCTGGTGTCCGAGCTGGCCGAGGCATCCCGCATACGCCATTGCCCACGGCGTCGCCCTGAACACGGACTATTACTTCTCCCACCTGTTGGGGGCGGCGTGCGTGACATTCAAGGCCCTGTTTGGGAATAACGCCAAGATCACCGAGAGTCTGTTAAAAAGGTTTATTCCCGAAGTGTGGCACCCCCCGGACGACGTGGCCGCGCGGCTCCGGGCCGCAGGGTTCGGGGCGGTGGGTGCCGGCGCTACGGCGGAGGAAACTCGTCGAATGTTGCATAGAGCCTTTGATACTCTAGCATGAGCCCCCCGTCGAAGCTGATGTCCCTCATTTTACAATAAATGTCTGCGGCCGACACGGTCGGAATCTCCGCGTCCGTGGGTTTCTCTGCGTTGCGCCGGACCACGAGCACAAACGTGCTCTGCCACACGTGGGCGACGAACCGGTACCCCGGGCACGCGGTGAGCATCCGGTCTATGAGCCGGTAGTGCAGGTGGGCGGACGTGCCGGGAAAGATGACGTACAGCATGTGGCCCCCGTAAGTGGGGTCCGGGAAAACAACAGCCGCGGGTCGCACGCCCCGCCTCCGCGCAGGATCGTGTGGACGAAAAAAAGTCGGGTGGCAAGAATCCCGGCCAAGAGGTCCTGGAGGGGGGCGTTGTGGCGGTCGGCCAACACGACCAAGGAGGCCAGGAAGGCGCGATGCTCGAATATCGTGTTGATCTGCTGCACGAAGGCCAGGATTAGGGCCTCGCGGCTGGTGGCGGCGAACCGCCCGTCTCCCGCGTTGCACGCGGGACAGCAACCCCCGATGCCTAGGTAGTAGCCCATCCCGGAGAGGGTCAGGCAGTTGTCGGCCACGGTCTGGTCCAGACAGAAGGGCAGCGACACGGGAGTGGTCTTCACCAGGGGCACCGAGAACGAGCGCACGATGGCGATCTCCTCGGAGGGCGTCTGGGCGAGGGCGGCGAAAAGGCCCCGATAGCGCTGGCGCTCGTGTAAACACAGCTCCTGTTTGCGGGCGTGAGGCGGCAGGCTCTTCCGGGAGGCCCGACGCCCACGCCCAGAGTCCCGCCGGCCGCAGAGGAGCACGACCGCCGGCGCTCCTTGCCGTGATAGGGCCCGGGCCGGGAGCCGCGGCGATGGGGGTCGGTATCATACATAGGTACACAGGGTGTGCTCCAGGGACAGGAGCGAGATCGAGTGGCGTCTAAGCAGCGCGCCCGCCTCACGGACAAATGTGGCGAGCGCGGTGGGCTTTGGTACAAATACCTGATACGTCTTGAAGGTGTAGATGAGGGCACGCAACCGCTATGCAGACACGCCCCTCGAACTCGTTCCCGCAGGCCAGCTTGGCCTTGTGGAGCAGCAGCTCGTCGGGATGGGTGGCGGGGGGATGGCCGAACAGAACCCAGGGGTCAACCTCCATCTCCGTGATGGCGCACATGGGGTCACAGAACATGTGCTTAAAGATGGCCTCGGGCCCCGCGGCCCGCAGCAGGCTCACAAACCGCCCGTCCCCGGGCTGCGTCTCGGGGTCCGCCTCGAGCTGGTCGACGACGGGTACGATACAGTCGAAGAGGCTCGTGTTGTTTTCCGAGTAGCGGACCACGGAGGCCCGGAGTCTGCGCAGGGCCAGCCAGTAAGCCCGCACCAGTAACAGGTTACACAGCAGGCATTCTCCGCCGGTGCGCCCGCGCCCCCGGCCGTGTTTCAGCACGGTGGCCATCAGAGGGCCCAGGTCGAGGTCGGGCTGGGCATCGTGTTCGGTAAACTGCGCAAAGCGCGGAGCCACGTCGCGCGTGCGTGCCCCGCGATGCGCTTCCCAGGACTGGCGGACCGTGGCGCGACGGGCCTCCGCGGCAGCGCGCAGCTGGGGCCCCGACTCCCAGACGGCGGGGGTGCCGGCGAGGGCAGCAGGCCAGATCCGCGTACGCCCACGTATCCGGCGACTCCTCCGGCTCGCGGTCCCCGGCGACCGTCTCGAATTCCCCGTTGCGAGCGGCGGCGCGCGTACAGCAGCTGTCCCCGCCCCCGCGCCGACCCTCCGTGCAGTCCAGGAGACGGGCGCAATCCTTCCAGTTCATCAGCGCGGTGGTGAGCGACGGCTGCGTGCCGGATCCCGCCGCCGACCCCGCCCCCTCCTCGCCCCCGGAGGCCAAGGTTCCGATGAGGGCCCGGGTGGCAGACTGCGCCAGGAACGAGTAGTTGGAGTACTGCACCTTGGCGGCTCCCGGGGAGGGCGAGGGCTTGGGTTGCTTCTGGGCATGCCGCCCGGGCACCCCGCCGTCGGTACGGAAGCAGCAGTGGAGAAAAAAGTGCCGGTGGATGTCGTTTATGGTGAGGGCAAAGCGTGCGAAGGAGCCGACCAGGGTCGCCTTCTTGGTGCGCAGAAAGTGGCGGTCCATGACGTACACAAACTCGAACGCGGCCACGAAGATGCTAGCGGCGCAGTGGGGCGCCCCCAGGCATTTGGCACAGAGAAACGCGTAATCGGCCACCCACTGGGGCGAGAGGCGGTAGGTTTGCTTGTACAGCTCGATGGTGCGGCAGACCAGACAGGGCCGGTCCAGCGCGAAGGTGTCGATGGCCGCCGCGGAAAAGGGCCCGGGGTCCAAAAGCCCCTCCCCACAGGGATCCGGGGGCGGGTTGCGGGGTCCTCCGCGCCCGCCCGAACCCCCTCCGTCGCCCGCCCCCCCGCGGGCCCTTGAGGGGGCGGTGACCACGTCGGCGGCGACGTCCTCGTCGAGCGTACCGACGGGCGGCACACCTATCACGTGACTGGCCGCCAGGAGCTCGGCGCAGAGAGCCTCGTTAAGAGCCAGGAGGCTGGGATCGAAGGCCACATACGCGCGCTCGAACGCCCCCGCCTTCCAGCTGCTGCCGGGGGACTCTTCGCACACCGCGACGCTCGCCAGGACCCCGGGGGGCGAAGTTGCCATGGCTGGGCGGGAGGGGCGCACGCGCCAGCGAACTTTACGGGACACAATCCCCGACTGCGCGCTGCGGTCCCAGACCCTGGAGAGTCTAGACGCGCGCTACGTCCGCGAGACGGCGCGCATGACGCGGCCGTCTGGTTCGAGGATATGACCCCCGCCGAGCTGGAGGTTGTCTTCCCGACTACGGACGCCAAGCTGAACTACCTGTCGCGGACGCAGCGGCTGGCCTCCCTCCTGACGTACGCCGGGCCTATAAAAGCGCCCGACGACGCCGCCGCCCCGCAGACCCCGGACACCGCGTGTGTGCACGGCGAGCTGCTCGCCCGCAAGCGGGAAAGATTCGCGGCGGTCATTAACCGGTTCCTGGACCTGCACCAGATTCTGCGGGGCTGACGCGCGCGCTGTTGGGTGGGACGGTTCGCGAACCCTTTGGTGGGTTTACGCGGGCACGCACGCTCCCATCGCGGGCGCCATGGCGGGACTGGGCAAGCCCTACCCCGGCCACCCAGGTGACGCCTTCGAGGGTCTCGTTCAGCGAATTCGGCTTATCGTCCCATCTACGTTGCGGGGCGGGGACGGGGAGGCGGGCCCCTACTCTCCCTCCAGCCTCCCCTCCAGGTGCGCCTTTCAGTTTCATGGCCATGACGGGTCCGACGAGTCGTTTCCCATCGAGTATGTACTGCGGCTTATGAACGACTGGGCCGAGGTCCCGTGCAACCCTTACCTGCGCATACAGAACACCGGCGTGTCGGTGCTGTTTCAGGGGTTTTTTCATCGCCCACACAACGCCCCCGGGGGCGCGATTACGCCAGAGCGGACCAATGTGATCCTGGGCTCCACCGAGACGACGGGGCTGTCCCTCGGCGACCTGGACACCATCAAGGGGCGGCTCGGCCTGGATGCCCGGCCGATGATGGCCAGCATGTGGATCAGCTGCTTTGTGCGCATGCCCCGCGTGCAGCTCGCGTTTCGGTTCATGGGCCCCGAAGATGCCGGACGGACGAGACGGATCCTGTGCCGCGCCGCCGAGCAGGCTATTACCCGTCGCCGCCGAACCCGGCGGTCCCGGGAGGCGTACGGGGCCGAGGCCGGGCTGGGGGTGGCTGGAACGGGTTTCCGGGCCAGGGGGGACGGTTTTGGCCCGCTCCCCTTGTTAACCCAAGGGCCCTCCCGCCCGTGGCCCAGGCCCTGCGGGGTCTTAAGCCCTACGGATTGGCCCCCCCGCGCTCGTTTTGGCGGCGGGACTCGTCCTGGGGGCCGCTATTTGGTGGGTGGTTGGTGCTGGCGCGCGCCTATAAAAAAGGACGCACCGCCGCCCTAATCGCCAGTGCGTTCCGGACGCCTTCGCCCCACACAGCCCTCCCGTCCGACACCCCCATATCGCTTCCCGACCTCCGGTCCCGATGGCCGTCCCGCAATTTCACCGCCCCAGCACCGTTACCACCGATAGCGTCCGGGCGCTTGGCATGCGCGGGCTCGTCTTGGCCACCAATAACTCTCAGTTTATCATGGATAACAACCACCCGCACCCCCAGGGCACCCAAGGGGCCGTGCGGGAGTTTCTCCGCGGTCAGGCGGCGGCGCTGACGGACCTTGGTCTGGCCCACGCAAACAACACGTTTACCCCGCAGCCTATGTTCGCGGGCGACGCCCCGGCCGCCTGGTTGCGGCCCGCGTTTGGCCTGCGGCGCACCTATTCACCGTTTGTCGTTCGAGAACCTTCGACGCCCGGGACCCCGTGAGGCCCGGGGAGTTCCTTCTGGGGAAAACACCCCACAGCAAAAAAATCAATAAAAGACCACACCAACGCACGAGCCTTGCGTTTAATGTCGAGGGGTTTATTCAAGGGAGTGGGATAGGGTTCGACGGTTCGAAACTTAACACACAAAATAATCGAGCGCGTCTAGCCCAGTAACATGTGCACGTGATGTAGGCTGGTCAGCACGGCGTCGCTGTGATGAAGCAGCGCCCGGCGGGTCCGCTGTAACTGCTGTTGTAGGCGGTAACAGGCGCGGATCAGCACCGCCAGGGCGCTACGACCGGTGCGTTGCACGGAGCGTCGCGACAGAACTGCGTTTGCCGATACGGGCGGGGGGCCGAATTGTAAGCGCGTCACCTCTTGGGAGTCATCGGCGGATAACGCACTGAATGGTTCGTTGGTTATGGGGGAGTGTGGTTCCCGAGGGAGTGGGTCGAGCGCCTCGGCCTCGGAATCCGAGAGGAACAACGAGGTGGTGTCGGAGTCTTCGTCGTCAGAGACATACAGGGTCTGAAGCAGCGACACGGGCGGGGGGGTAGCGTCAATGTGTAGCGCGAGGGAGGATGCCCACGAAGACACCCCAGACAAGGAGCTGCCCGTGCGTGGATTTGTGGACGACGCGGAAGCCGGGACGGATGGGCGGTTTTGCGGTGCCCGGAACCGAACCGCCGGATACTCCCCGGGTGCTACATGCCCGTTTTGGGGCTGGGGTTGGGGCTGGGGTGGGGCTGGGGTTGACGGGTTGGGGCTGGGGCTGGGGCTGGGGTTGGGGCTGGGGTTGGGGTTGGGGCTGGGGTTGGGGTTGGGGCTGGGGTTGGGGCTGGGGGGCTGGGGCGCGGACAGGCGGTTGACGGGCAAATGCCCCCGGGGGCGCGCAGATGTGGGGGCGTGGCCACCGGCTGCCGGGTAGTGGGGCGGCGGGAAACCGGGCCTCCGGGCGTAACACCGCCCTCCAGCGTCAAGTATGTGGGGGGCGGGCCTGACGTCGGGGGCGGGGTGACGGGTTGGACCGCGGGAGGCGGGGGAGAGGGACCTGCGGGAGAGGATGAGGTCGGCTCGGCCGGGTTGCGGCCTAAAACAGGGGCCGTGGGGTCGGCGGGGTCCCAGGGTGAAGGGAGGGATTCCCGCGATTCGGACAGCGACGCGACAGCGGGGCGCGTAAGGCGCCGCTGCGGCCCGCCTACGGGAACCCTGGGGGGGGTTGGCGCGGGACCCGAGGTTAGCGGGGGGCGGCGGTTTTCGCCCCCGGGCAAAACCGTGCCGGTTGCGACCGGGGGCGGAACGGGATCGATAGGGAGAGCGGGAGAAGCCTGGCCGGCGAACTGGGGACCGAGCGGGAGGGGCACACCAGACACCAAAGCGTGGAGCGCTGGCTCTGGGGGTTTGGGAGGGGCCGGGGGGCGCGCGAAATCGGTAACCGGGGCGACCGTGTCGGGGAGGGCAGGCGGCCGCCAACCCTGGGTGGTCGCGGAAGCCTGGGTGGCGCGCGCCAGGGAGCGTGCCCGGCGGTGTCGGCGCGCGCGCGACCCGGACGAAGAAGCGGCAGAAGCGCGGGAGGAGGCGGGGGGGCGGGGGGCGGGGCGGGGGGACGGCAAGCGCCGGAAGTCGTCGCGGGGGCCCACGGGCGCCGGCCGCGGCTTTCGGCCGGGACGCCCGGTCGTGCTTCGCGAGCCGGGACTGCCGGCCCAGGGGGCCGCGGTGCACACTGGGACGTGGGGAAGGGGGCCGGGGCAAGGAGGGGCGCGGGGCCGCCGGAGTCGTCAGACGCGAGCTCCTCCAGGCCGTGAATCCATGCCCACATGCGAGGGGGGACGGGCTCGCCGGGGGTGGCGTCGGTGAATAGCGTGGGGGCCAGGCTTCCGGGCCCCAACGAGCCCTCCGTCCCAACAAGGTCCGCCGGGCCGGGGGTCGGGTTCGGGACCGAGGGGCTCTGGTCGTCGGGGGCGCGCTGGTACACCGGATGCCCCGGGATAGCTCCCCCGACAGGAGGGAGGCGTCGAACGGCCGCCCGAGGATAGCTCGCGCGAGGAAGGGGTCCTCGCGGTGGCGCTGGCGGCGAGGACGTCCTCGCCGCCCGCCACAAACGGGAGCTCCTCGGTGGCCTCGCTGCCAACAAACCGCACGTCGGGGGGGCCGGGGGGGTCCGGGTTTTCCCACAACACCGCGACCGGGGTCATGGAGATGTCCACGAGCACCAGACACGGCGGGCCCCGGGCGGGGGGGGTCCGGGTTTTCCCACAACACCGCGACCGGGGTCATGGAGATGTCCACGAGCACCAGACACGGCGGGCCCCGGGCGAGGGGCCGCTCGGCGATGAGCGCGGACAGGCGCGGGAGCTGTGCCGCCAGACACGCGTTTTCAATCGGGTTCAGGTCGGCGTGCAGGAGGCGGACGGCCCACGTCTCGATGTCGGACGACACGGCATCGCGCAAGGCGGCGTCCGGCCCGCGAGCGCGTGAGTCAAACAGCGTGAGACACAGCTCCAGCTCCGACTCGCGGGAAAAGGCCGTGGTGTTGCGGAGCGCCACGACGACGGGCGCGCCCAGGAGCACTGCCGCCAGCACCAGGTCCATGGCCGTAACGCGCGCCGCGGGGGTGCGGTGGGTGGCGGCGGCCGGCACGGCGACGTGCTGGCCCGTGGGCCGGTAGAGGGCGTTGGGGGGAGCGGGGGGTGACGCCTCGCGCCCCCCCGAGGGGCTCAGCGTCTGCCCAGATTCCAGACGCGCGGTCAGAAGGGCGTCGAAACTGTCATACGGTAGTCGGCGCGCCCCCCGAGGGGCTCAGCGTCTGCCCAGATTCCAGACGCCTCCGGCGTCGAAACTGTCATACTCTGTGTAGTCGTCCGGAAACATGCAGGTCCAAAGAGCGGCCAGGGCGGTGCTTGGGAGACACATGCGCCCGAGGACGCTCACCGCCGCCAGCGCCTGGGCGGGACTCAGCTTTCCCAGCGCGGCGCCGCGCTCGGTTCCCAGCTCGGGGACCGAGCGCCAGGGCGCCAGGGGGTCGGTTTCGGACAACTTGCCGCGGCGCCAGTCTGCCAGCCGCGTGCCGAACATGAGGCCCCGGGTCGGAGGGCCTCCGGTCTATAATCTGGCAGCCGCGGATGCGGGCGTCTGGATGCGGGGTCAGGCGCTGCACGAATAGCATGGAATCTGCTGCGTTCTGAAACGCACGGGGGAGGGTGAGATGCATGTACTCGTGTTGGCGGACCAGATCCAGGCGCCAAAAGGTGTAAATGTGTTCCGGGGAGCTGGCCACCAGCGCCACCAGCACGTCGTTCTCGTTAAAGGAAACGCGGTGCCTAGTGGAGCTGTGGGGCCCGAGCGGCGGTCCCGGGGCCGCCGCGTCACCCCCCCATTCCAGCTGGGCCCAGCGACACCCAAACTCGCGCGTGAGAGTGGTCGCGACGAGGGCGACGTAGAGCTCGGCCGCCGCATCCATCGAGGCCCCCCATCTCGCCTGGCGGTGGCGCACAAAGCGTCCGAAGAGCTGAAAGTTGGCGGCCTGGGCGTCGCTGAGGGCCAGCTGAAGCCGGTTGATGACGGTGATGACGTACATGGCCGTGACGGTCGAGGCCGACTCCAGGGTGTCCGTCGGAAGCGGGGGGCGAATGCATGCCGCCTCGGGACACATCAGCAGCGCGCCGAGCTTGTCGGTCACGGCCGGGAAGCAGAGCGCGTACTGCAGTGGCGTTCCATCCGGGACCAAAAAGCTGGGGGCGAACGGCCGATCCAGCGTACTGGTGGCCTCGCGCAGCACCAGGGGCCCCGGGCCTCCGCTCACTCGCAGGTACGCCTCGCCCCGGCGGCGCAGCATCTGCGGGTCGGCCTCTTGGCCGGGTGGGGCGGACGCCCGGGCGCGTGCGTCTCGGGCGCGAAGATCCACGAGCAGGGGCGCGGGCGCGGCGGCCGCGCCCGCGCCCGTCTGGCCTGTGGCCTTGGCGTACGCGCTATATAAGCCCATGCGGCGTTGGATGAGCTCCCGCGCGCCCCGGAACTCCTCCACCGCCCATGGGGCCAGGTCCCCGGCCACCGCGTCGAATTCCGCCAACAGGCCCCCCAGGGTGTCAAAGTTCATCTCCCAGGCCACCCTTGGCACCACCTCGTCCCGCAGCCGGGCGCTCAGGTCGGCGTGTTGGGCCACGCGCCCCCCGAGCTCCTCCACGGCCCCGGCCCGCTCGGCGCTCTTGGCGCCCAGGGCGCCCTGGTACTTGGCGGGAAGGCGCTCGTAGTCCCGCTGGGCTCGCAGCCCCGACACAGTGTTGGTGGTGTCCTGCAGGGCGCGAAGCTGCTCGCATGCCGCGCGAAATCCCTCGGGCGATTTCCAGGCCCCCCCGCGAACGCGGCCGAAGCGACCCCATACCTCGTCCCACTCCGCCTCGGCCTCCTCGAGAGACCTCCGCAGGGCCTCGACGCGGCGACGGGTGTCGAAGAGCGCCTGCAGGCGCGCGCCCTGTCGCGTCAGGAGGCCCGGGCCGTCGCCGCTGGCCGCGTTTAGCGGGTGCGTCTCAAAGGTACGCTGGGCATGTTCCAACCAGGCGACCGCCTGCACGTCGAGCTCGCGCGCCTTCTCCGTCTGGTCCAACAGAATTTCGACCTGATCCGCGATCTCCTCCGCCGAGCGCGCCTGGTCCAGCGTCTTGGCCACGGTCGCCGGGACGGCGACCACCTTCAGCAGGGTCTTCAGATTGGCCAGACCCTCGGCCTCGAGCTGGGCCCGGCGCTCGCGCGCGGCCAGCACCTCCCGCAGCCCCGCCGTGACCCGCTCGGTGGCTTCGGCGCGCGCTGTTTGGCGCGCACCACGCGTCCTTGGTATCGGCCAGGCCCTGTCGGGTCACGAATGCGACGTAGTCGGCGTACGCCGTGTCCTTCACGGGGCTCTGGTCCACGCGCTCCAGCGCCGCCACGCACGCCACCAGCGCGTCCTCGCTCGGGCAGGGCAGGGTGACCCCTGCCCGGACAAGCTCGGCGGCCGCCGCCGGGTCGTTGCGCACCGCGGATATCTCCTCCGCGGCGGCGGCCAGGTCCAGCGCCACGCTTCCGATCGCGCGCCGCGCGTCGGCCCGGAGGGCGTCCAGGCGATCGCGGATATCCACGTACTCGGCGTAGCCCTTTTGAAAAAACGGCACGTACTGGCGCAGGGCCGGCACGCCCCCCAAGTCTTCCGACAGGTGTAGGACGGCCTCGTGGTAGTCGATAAACCCGTCGTTCGCCTGGGCCCGCTCCAGCAGCCCCCCCGCCAGCCGCAGAAGCCGCGCCAGGGGCTCGGTGTCCACCCGAAACATGTCGGCGTACGTGTCGGCCGCGGCCCCGAAGGCCGCGCTCCAGTCGATGCGGTGAATGGCTGCGAGCGGGGGGAGCATGGGGTGGCGCTGGTTCTCGGGGGGGTATGGGTTAAACGCAAGGGCCGTCTCCAGGGCAAGGGTCACCGCCTTGGCGTTGGTTCCCAGCGCCTGTTCGGCCCGCTTTCGGAAGTCCCGGGGGTTGTAGCCGTGCGTGCCCGCCAGCGCCTGCAGGCGACGGAGCTCGACCACGTCAAACTCGGCACCGCTTTCCACGCGGTCCAGCACGGCCTCCACGTCGGCGGCCCAGCGCTCGTGGCTACTGCGGGCGCGCTGGGCCGCCATCTTCTCTCTCAGGTCGGCGATGGCGGCCTCAAGTTCGTCGGCGCGGCGTCGCGTGGCGCCGATGACCTTTCCCAGCTCCTGCAGGGCGCGCCCGCTGGGGGAGTGGTCCCCGGCCGTCCCTTCGGCGTGCAACGGCCCCCGAACCTGCCCTCGTGGCCCGCGAGGCTTTCCCGCGCGCCGGTGGTCGCGCGCGTCGCGGCCTGGATCAGGGAGGCATGCTCTCCCTCCGGTTGGTTGGCGGCCCGGCGCACCTGGACGACAAGGTCGGCTGCCGCCGACCCTAAGGTCGTGAGCTGGGCGATGGCCCCCCGCGCGTCCAGGGCCAACCGAGTCGCCTTGACGTATCCCGCGGCGCTGCGGCCATGGCCGCTAGGAAGGCCAGGGGGGAGGCCGGGTCGCTGGCGGCCGCGCCCAGGGCCGTCACCGCGTCGACCAGGACGCGGTGCGCCCGCACGGCCGCATCCACCGTCGACGCGGGGTCTGCCGTCGCGACGGCGGCGCTGCCGGCGTTGATGGCGTTCGAGACGGCGTGGGCTATGATCGGGGCGTGATCGGCGAAGAACGCAAGGAAACGGAGTCTCTGGGGCGTCGGCGACAGGTTCTTCAGCACCACCACGAAGCTGGGATGCAAGCCAGACAGAGCCGCGCCGTGCCCGGGACGGGTGCTCCAGGGCATCTCGGTACTGCCCCAGCAGCCCCCACATGTCCGCCCGCAGCGCCGCCGTAACCTCAGGGGGCGCCCCCCGAACGGCCTCGGGGAGGTCCGACCAGCCCGCCGGCAGGGAGGCCCGCAGGGTCGCCAGGACGGCCGGACAGGCCTTTAGCCCCACAAAGTCAGGGAGGGGGCGCAGGACCCCCTGGAGTTTGTGCAAGAACTTCTCCCGGGCGTCGCGGGCCACCTTCGCCCGCTCCCGCGCTCCCTCGAGCATTGCCTCCAGGGAGCGCGCGCGCTCCCGCAAACGGGCACGCGCATCGGGGGCGAGCTCTGCCGTCAGCTTGGCGGCATCCATGGCCCGCGCCTGCCGCAGCGCTTCCCGGCCATGCGCGTGGCCTCTGGCGACAGCCCGCCGTCGTCGGGGTAGGGCGACGCGCCGGGCGCAGGAACAAAGGCCGCGTCGCTGTCCAGCTGCTGGCCCAGGGCCGCATCTAGGGCGTCGAAGCGCCGCAGCTCGGCCAGACCCGAGCTGCGGCGCGCCTGCTGGTCGTTAATGTCGCGGATGCTGTGCGCCAGCTCGTCCAGCGGCTTGCGTTCTATCAGCCCTTGGTTGGCGGCGTCCGTCAGGACGGAGAGCCAGGCCGCCAGGTCCTCGGGGGCGTCCAGCGTCTGGCCCCGCTGGATCAGATCCCGCAACAGGATGGCCGTGGGGCTGGTCGCGATCGGGGGCGGGGCGGGCGCGCCGGGCGCAGGAACAAAGGCCGCGTCGCTGGCCAGCTGCTGGCCCAGGGCCGCATCTAGGGCGCGAAGCGCCGCGGCGCGGCCGGCCCCGGGCGGGGGCGCGCCTGCTGGTCGTTAATGTCGCGGATGCTGTGCGCCAGCTCGTCCAGCGGCTTGCGTTCTATCAGCCCTTGGTTGGCGGCGTCCGTCAGGACGGAGAGCCGGCCGCCGGTCCTCGGGGGCGTCCAGCGTCTGGCCCCGCTGGATCAGATCCCGCAACAGGATGGCCGTGGGGCTGGTCGCGATCGGGGGCGGGGCGGGAATGGCGGCGCGCTGCGCGATGTCCCGCGGTGCTGGTCGAAGACAGGCAGGGACTCGAGCAGCTGGACCACGGGCACGACGGCGGCCGAAGCCACGTGAAACCGGCGGTCGTTGTTGTCGCTGGCCTGTAGAGCCTTGGCGCTGTATACGGCCCCCCGGTAAAAGTACTCCTTAACCGCGCCCTCGATCGCCCGACGGGCCTGGGTCCGCACCTCCTCCAGCCGAACCTGAACGGCCTCGGGGCCCAGGGGGGGTGGGCGCGGAGCCCCCTGCGGGGCCGCCCCGCCGGGGGAAGTAAGAAGAGGGGCCCGGCGTGCTGTGAGACCGCGTCGACCCCGCGAGCGAGGGCGTCGAGGGCCTCGCGCATCTGGCGATCCTCCGCCTCCACCCTAATCTCTTCGCCACGGGCAAATTTGGCCAGAGCCTGGACTCTATACAGAAGCGGTTCTGGGTGCTTCGGGGTGGCGGGGGCAAAAAGGGTGTCCGGGTGGGCCTGCGAGCGCTCCAGAAGCCACTCGCCGAGGCGTGTATACAGATTGGCCGGCGGGGCCGCGCGAAGCTGCAGCTCCAGGGCCGCGAGTTCCCCGTAAAAGGCGTCCGTCTCCCGAATGACATCCCTAGCCACAAGGATCAGCTTCGCCAGCGCCAGGCGACCGATCAGAGAGTTTTCGTCCAGCACGTGCTGGACGAGGGGCAGATGGGCGGCCACGTCGGCCAGGCTCAGGCGCGTGGAGGCCAGAAAGTCCCCCACGGCCGTTTTCCGGGGCAGCATGCTCAGGGTAAACTCCAGCAGGGCGGCGGCCGGGCCGGCCACCCCGGCCTGGGGGTGCGTCCGGGCCCCGTTCTCGATGAGAAAGGCGAGGACGCGTTCAAAGAAAAAAATAACACAGAGCTCCAGCAGCCCCGGAGAAGCCGGATACGGCGACCGTAAGGCGCTGATGGTGAGCCGCGAACACGCGGCGCCCTCGCGGGCCAGGGTGGCGGAGCACGCGGTGAACTTAACCGCCGTGGCGGCCACGTTTGGGTGGGCCTCGAACAGCTGGGCGAGGTCTGCGCCCGGGGGCTCGGGTGAGCGGCGAGTCTTCAGCGCCTCGAGGGCCTGTGAGGACGCCGGAACCATGGGCCCGTCGTCCTCGCCCGCCTCGGCGACCGGCGGCCCGGCCGGGTCGGGGGGTGCCGAGGCGAGGACAGGCTCCGGAACGGAGGCGGGGACCGCGGCCCCGACGGGGGTTTTGCCTTTGGGGGTGGATTTCTTCTTGGTTTTGGCAGGGGGGGCCGAGCGTTTCGTTTTCTCCCCCGAAGTCAGGTCTTCGACGCTGGAAGGCGGAGTCCAGGTGGGTCGGCGGCGCTTGGGAAGGCCGGCCGAGTAGCGTGCCCGGTGCCGACCAACCGGGACGACGCCCATCTCCAGGACCCGCATGTCGTCGTCATCTTCTTCGGCCGCCTCTGCGGCGGGGGTCTTGGGGGCGGAGGGAGGCGGTGGTGGGATCGCGGAGGGTGGGTCGGCGGAGGGGGGATCCGTGGGTGGGGTACCCTTTAGGGCCACCGCCCATACATCGTCGGGCGCCCGATTCGGGCGCTTGGCCTCTGGTTTTGCCGACGGACCGGCCGTCCCCCGGGATGTCTCGGAGGCCCTGTCGTCGCGACGGGCCCGGGTCGGTGGCGGCGACTGGGCGGCTGTGGGCGGGTGTGGCCCCGGCCCCCCTCCCCCCTCCCGGGGGCCCACGCCGACGCAGGGCTCCCCCAGGCCCGCGATCTCGCCCCGCAGGGGGGGCGTGATGGCCACGCGCCGTTCGCTGAACGCTTCGTCCTGCATGTAAGTCTCGCTGGCCCCGTAAAGATGCAGAGCCGCGGCCGTCAAGTCCGCAGGAGCCGCGGGTTCCGGGCCCGACGGCACGAAAAACACCATGGCTCCCGCCCACCGTACGTCCGGGCGATCGCGGGTGTAATACGTCAGGTATGGATACATGTCCCCCGCCCGCACTTTGGCGATGAACGCGGGGGTGCCCTCCGGAAGGCCATGCGGGTCAAAAGGTAGGCGGTGTCGCCGTCCCTGAACAGCCCCATCCCTAGGGGGCCAATGGTTAGGAGCGTGTACGACAGGGGGCGCAGGGCCCACGGGCCGGCGAAGAACGTGTGTGCGGGGCATTGTGTCTCCAGCAGGCCTGCCGCGGGCTCCCCGAAGAAGCCCACCTCGCCGTATACGCGCGAGAAGACACAGCGCAGTCCGCCGCGCGCCCCTGGGTACTCGAGGAAGTTGGGGAGCTCGACGATCGAACACATGCGCGGCGGCCCAGGGCCCGCAGTCGCGCGCGTCCACTCGCCCCCCTCGACCAAACATCCCTCGATGGCCTCCGCGGACAGAACGTCGCGAGGGCCCACATCAAATATGAGGCTGAGAAAGGCAGCGACGAGCGCATGCACGATACCGACCCCCCCGGCTCCAGGTCGGGCGCGAACTGGTTCCGAGCACCGGTGACCACGATGTCGCGATCCCCCCCGCGTTCCATCGTGGAGTGCGGTGGGGTGCCCGCGATCATATTGCCCTGCGGGCCAGAGACCCGGCCTGTTTATGGACCGGACCCCCGGGGTTAGTGTTGTTTCCGCCACCCACGCCCCCGTACCATGGCCCCGGTTCCCCTGATTAGGCTACGAGTCGCGGTGATCGCTTCCCAAAAACCGAGCTGCGTTTGTCTGTCTTGGTCTTCCCCCCCCCCAGCCCGCACACCATAACACCGAGAACAACACACGGGGGTGGGCGGAACATAATAAAGCTTTATTGGTAACTAGTTAACGGCAAGTCCGTGGGTGGCGCGACGGTGTCCTCCGGGATCATCTCGTCGTCCTCGACGGGGGTGTTGGAATGAGGCGCCTCCTCGCGGTCCACCTGGCGTGGGCCGTGCCCATAGGCCTCCGGCTTCTGTGCGTCCATGGGCGTAGGCGCGGGGAGACTGTTTCCGGCGTCGCGGACCTCCAGGTCCCTGGGAGCCTCCGGTCCGGCTAACGGACGAAACGCGGAAGCGCGAAACACGCCGTCGGTGACCCGCAGGAGCTCGTTCATCAGTAACCAATCCATACTCAGCGTAACGGCCAGCCCCTGGCGAGACAGATCCACGGAGTCCGGAACCGCGGTCGTCTGGCCCAGGGGGCCGAGGCTGTAGTCCCCCCAGGCCCCTAGGTCGCGACGGCTCGTAAGCACGACGCGGTCGGCCGCGGGGCTTTGCGGGGGGGCGTCCTCGGGCGCATGCGCCATTACCTCTCGGATGGCCGCGGCGCGCTGGTCGGCCGAGCTGACCAAGGGCGCCACGACCACGGCGCGCTCCGTCTGCAGGCCCTTCCACGTGTCGTGGAGTTCCTGGACAAACTCGGCCACGGGCTCGGGTCCCGCGGCCGCGCGCGCGGCTTGATAGCAGGCCGACAGACGCCGCCAGCGCGCTAGAAACTGACCCATGAAACAACCCCCGTGTACCTGGTCTCCCGACAGCAGCTTCGACGCCCGGGCGTGAATGCCGGCCACGACGGACAGAAACCCGTGAATTTCGCGCCGGACCACGGCCAGCACGTTGTCCTCGTGCGACACCTGGGCCGCCAGCTCGTCGCACACCCCCAGGTGCGCCGTGGTTTCGGTGATGACGGAACGCAGGCTCGCGAGGGACGCGACCAGCGCGCGCTTGGCGTCGTGATACATGCTGCAGTACTGACTCACCGCGTCCCCCATGGCCTCGGGGGGCCAGGGCCCCAGGCGGTCGGGCGTGTCCCCGACCACCGCATACAGGCGGCGCCCGTCGCTCTCGAACCGACACTCGAAAAAGGCGGAGAGCGTGCGCATGTGCAGCCGCAGCAGCACGATGGCGTCCTCCAGTTGGCGAATCAGGGGGTCGGCGCGCTCGGCGAGGTCCTGCAGCACCCCCCGGGCAGCCAGGGCGTACATGCTAATCAACAGGAGGCTGGTGCCCACCTCGGGGGGCGGGGGGGGCTGCAGTTGGACCAGGGGCCGCAGCTGCTCGACGGCACCCCTGGAGATCACGTACAGCTCCCGGAGCAGCTGCTCTATGTTGTCGGCCATCTGCATAGTGGGGCCGAGGCCGCCCCGGGCGGCCGGTTCGAGGAGAGTGATCAGCGCGCCCAGTTTGGTGCGATGGCCCTCGACCGTGGGGAGATAGCCCAGCCCAAAGTCCCGGGCCCAGGCCAACACACGCAGGGCGAACTCGACCGGGCGGGGAAGGTAGGCCGCGCTACACGTGGCCCTCAGCGCGTCCCCAACCACCAGGGCCAGAACGTAGGGGACGAAGCCCGGGTCGGCGAGGACGTTGGGGTGAATGCCCTCGAGGGCGGGGAAGCGGATCTGGGTCGCCGCGGCCAGGTGGACAGAGGGGGCATGGCTGGGCTGCCCGACGGGGAGAAGCGCGGACAGCGGCGTGGCCGGGGTGGTGGGGGTGATGTCCCAGTGGGTCTGACCATACACGTCGATCCAGATGAGCGCCGTCTCGCGGAGAAGGCTGGGTTGACCGGAACTAAAGCGGCGCTCGGCCGTCTCAAACTCCCCCACGAGCGCCCGCCGCAGGCTCGCCAGATGTTCCGTCGGCACGGCCGGCCCCATGATACGCGCCGCGTCTGGCTCAGAACGCCCCCCGACAGGCCGCCGCCTCACAGCGCCGCCCGTGCGTGTGCTCGCTGGCGCCCTGGCCCGCCTGAAAGTTTTTACGTAGTTGGCATAGTACCCGTATCCCGCGCCAGACCAAACACGTTCGCCCCCGCGAGGGCAATGCCCCAAAGAGCTGCTGGACTTCGCCGAGTCCGTGGCCGGCGGGCGTCCGCGCGGGGACGCCCGCCGCCAGAAACCCCTCCAGGGCCGAAAGGGAGTGCGTGCAGTGCGAGGGCGTGAACCCAGCGTCGATCAGGGTGTTGATCACCACGGAGGGCGAATTGGATTCTGGATCAACGTCCACGTCTGCTGCAGCAGAGCCAGCAGCCGCTGCTGGGCGCCGGCGGAGGGCTGCTCCCCGAGCTGCAGCAGGCTGGAGACGGCAGGCTGGAAGACTGCCAGTGCCGACGAACTCAGGAACGGCACGTCGGGATCAAACACGGCCACGTCCGTCCGCACGCGCGCCATTAGCGTCCCCGGGGGCGCACAGGCCGAGCGCGGGCTGACGCGGCTGAGGGCCGTCGACACGCGCACCTCCTCGCGGCTGCGAACCATCTTGTTGGCCTCCAGTGGCGGAATCATTATGGCCGGGTCGATCTCCCGCACGGTGTGCTGAAACTGCGCCAACAGGGGCGGCGGGACCACAGCCCCCCGCTCGGGGGTCGTCAGGTACTCGTCCACCAGGGCCAACGTAAAGAGGGCCCGTGTGAGGGGAGTGAGGGTCGCGTCGTCTATGCGCTGGAGGTGCGCCGAGAACAGCGTCACCCGATTACTCCCCCCAAGAACCGGAGGCCCTCTTGCACGAACGGGGCGGGGAAGAGCAGGCTGTACGCCGGGGTGGTAAGGTTCGCGCTGGGCTGCCCCAACGGGACCGGCGCCAGCTTGAGCGACGTCTCCCCAAGGGCCTCGATGGAGGTCCGCGGGCTCATGGCCAAGCAGCTCTTGGTGACGGTTTGCCAGCGGTCTATCCACTCCACGGCGCACTGCGGCGCGGACCGGCCCCAGGGCCGCCGCGGTGCGCAGGCCGGCGGACTCCAGCGCATGGGACGTGTCGGAGCCGGTGACCGCGAGGATGGTGTCCTTGATGACCTCCATCTCCCGGAAGGCCTGGTCGGGGGCCTCGGGGAGAGCCACCACCAAGCGGTGTACGAGCAACCCGGGGAGGTTCTCGGCCAAGAGCGCCGTCTCCGGAAGCCCGTGGGCCCGGTGGAGCGCGCACAGGTGTTCCAGCAGCGGCCGCCAGCATGCCCGCGCGTCTGCCGGGGCGATGGCCGTTCCCGACAACAGAAACGCCGCCATGGCGGCGCGCAGCTTGGCCGTGGCCAGAAACGCCGGGTCGTCCGCCCCGTTTGCCGTCTCGGCCGTGGGGGTTGGCGGTTGGCGAAGGCCGGCTAGGCTCGCCAATAGGCGCTGCATAGGTCCGTCCGAGGGCGGACCGGCGGGTGAGGTCGTGACGACGGGGGCCTCGGACGGGAGACCGCGGTCTGCCATGACGCCCGGCTCGCGTGGGGGGGGGACAGCGTAGACCAACGACGAGACCGGGCGGGAATGACTGTCGTGCGCTGTAGGGAGCGGCGAATTATCGATCCCCCGCGGCCCTCCAGGAACCCCGCAGGCGTTGCGAGTACCCCGCGTCTTCGCGGGGTGTTATACGGCCACTTAAGTCCCGGCATCCCGTTCGCGGACCCAGGCCCGGGGGATTGTCCGGATGTGCGGGCAGCCCGGACGGCGTGGGTTGCGGACTTTCGGCGGGGCGGCCCAAATGGCCCTTTAAACGTGTGTATACGGACGCGCCGGGCCAGTCGGCCAACACAACCCACCGGAGGCGGTAGCCGCGTTTGGCTGTGGGGTGGGTGGTTCCGCCTTGCGTGAGTGTCCTTTCGACCCCCCCCCTCCCCCGGGTCTTGCTAGGTCGCGATCTGTGGTCGCAATGAAGACCAATCCGCTACCCGCAACCCCTTCCGTGTGGGGCGGGAGTACCGTGGAACTCCCCCCCACCACACGCGATACCGCGGGGCAGGGCCTGCTTCGGCGCGTCCTGCGCCCCCCGATCTCTCGCCGCGACGGCCCAGTGCTCCCCAGGGGGTCGGGACCCCGGAGGGCGGCCAGCACGCTGTGGTTGCTTGGCCTGGACGGCACAGACGCGCCCCCTGGGGCGCTGACCCCCAACGCGATACCGAACAGGCCCTGGACAAGATCCTGCGGGGCACCATGCGCGGGGGGGCGGCCCTGATCGGCTCCCCGCGCCATCATCTAACCCGCCAAGTGATCCTGACGGATCTGTGCCAACCCAACGCGGATCGTGCCGGGACGCTGCTTCTGGCGCTGCGGCACCCCGCCGACCTGCCTCACCTGGCCCACCAGCGCGCCCCGCCAGGCCGGCAGACCGAGCGGCTGGGCGAGGCCTGGGGCCAGCTGATGGAGGCGACCGCCCTGGGGTCGGGGCGAGCCGAGAGCGGGTGCACGCGCGCGGGCCTCGTGTCGTTTAACTTCCTGGTGGCGGCGTGTGCCGCCTCGTACGACGCGCGCGACGCCGCCGATGCGGTACGGGCCCACGTCACGGCCAACTACCGCGGGACGCGGGTGGGGGCGCGCCTGGATCGTTTTTCCGAGTGTCTGCGCGCCATGGTTCACACGCACGTCTTCCCCCACGAGGTCATGCGGTTTTTCGGGGGGCTGGTGTCGTGGGTCACCCAGGACGAGCTAGCGAGCGTCACCGCCGTGTGCGCCGGGCCCCAGGAGGCGGCGCACACCGGCCACCCGGGCCGGCCCCGCTCGGCCGTGATCCTCCCGGCGTGTGCGTTCGTGGACCTGGACGCCGAGCTGGGGCTGGGGGGCCCGGGCGCGGCGTTTCTGTACCTGGTTCACTTACCGCCAGCGGGACCAGGAGCTGTGTTGTGTGTACGTGATCAAGAGCCAGCTCCCCCCGCGCGGGTTGGAGCCGGCCCTGGAGCGGCTGTTTGGGCGCCTCCGGATCCCAACACGATTCACGGCACCGAGGACATGACGCCCCCGGCCCCAAACCGAAACCCCGACTTCCCCCTCGCGGGCCTGGCCGCCAATCCCCAAACCCCGCGTTGCTCTGCTGGCCAGGTCACGAACCCCCAGTTCGCCGACAGGCTGTACCGCTGGCAGCCGGACCTGCGGGGGCGCCCCACCGCACGCACCTGTACGTACGCCGCCTTCGCAGAGCTCGGCATGATGCCCGAGGATAGTCCCCGCTGCCTGCACCGCACCGAGCGCTTTGGGGCGGTCAGCGTCCCCGTTGTCATCCTGGAAGGCGTGGTGTGGCGCCCCGGCGAGTGGCGGGCCTGCGCGTGAGCGTAGCAAACGCCCCGCCCACACAACGCTCCGCCCCCAACCCCTTCCCCGCTGTCACTCGTTGTTCGTTGACCCGGACGTCCGCCAAATAAAGCCACTGAAACCCGAAACGCGAGTGTTGTAACGTCCTTTGGGCGGGAGGAAGCCACAAAATGCAAATGGGATACATGGAAGGAACACACCCCCGTGACTCAGGACATCGGCGTGTCCTTTTGGGTTTCACTGAAACTGGCCCGCGCCCCACCCCTGCGCGATGTGGATAAAAAGCCAGCGCGGGTGGTTTAGGGTACCACAGGTGGGTGCTTTGGAAACTTGTCGGTCGCCGTGCTCCTGTGAGCTTGCGTCCCTCCCCGGTTTCCTTTGCGCTCCCGCCTTCCGGACCTGCTCTCGCCTATCTTCTTTGGCTCTCGGTGCGATTCGTCAGGCAGTGGCCTTGTCGAATCTCGACCCCACCACTCGCCGGACCCGCCGACGTCCCCTCTCGAGCCCGCCGAAACCCGCCGCGTCTGTTGAAATGGCCAGCCGCCCCGCCGCATCCTCTCCCGTCGAAGCGCGGGCCCCGGTTGGGGGACAGGAGGCCGGCGGCCCCAGCGCAGCCACCCAGGGGGAGGCCGCCGGGGCCCCTCTCGCCCGCGGCCACCACGTGTACTGCCAGCGAGTCAATGGCGTGATGGTGCTTTCCGACAAGACGCCCGGGTCCGCGTCCTACCGCATCAGCGATAGCAACTTTGTCCAATGTGGTTCCAACTGCACCATGATCATAGACGGAGACGTGGTGCGCGGGCGCCCCCAGGACCCGGGGGCCGCGGCATCCCCCGCTCCCTTCGTTGCGGTGACAAACATCGGAGCCGGCAGCGACGGCGGGACCGCCGTCGTGGCATTCGGGGGAACCCCACGTCGCTCGGCGGGGACGTCTACCGGTACCCAGACGACCGACGTCCCCACCGAGGCCCTTGGGGGCCCCCCTCCTCCTCCCCGCTTCACCCTGGGGGGCGGCTGTTGTTCCTGTCGCGACACACGGCGCCGCTCTGCGGGATTCGGGGGGGAGGGGGATCCCGTCGGCCCCGCGTTGTCGTCTCGGACGACCGTTGCTCCGATTCCGACTCGGATGACTCGGAGGACACCGACTCGGAGACGCTGTCACACGCCTCCTCGGACGTGTCCGGCGGGGCCACGTACGACGACGCCCTTGACTCCGATTCGTCATCGGATGACTCCCTGCAGATAGATGGCCCCGTGTGTCGCCCGTGGAGCAATGACACCGCGCCCCTGGATGTTTGCCCCGGGACCCCCGGCCCGGGCGCCGACGCCGGTGGTCCCTCAGCGGTAGACCCACACGCACCGACGCCAGGGGCCGGCGCTGGTCTTGCGGCCGATCCCGCCGTGGCCCGGGACGACGCGGAGGGGCTTTCGGACCCCCGGCCACGTCTGGGAACGGGCACGGCCTACCCCGTCCCCCTGGAACTCACGCCCGAGAACGCGGAGGCCGTGGCGCGCTTTCTGGGAGATGCCGTGAACCGCGAACCCGCGCTCATGCTGGAGTACTTTTGCCGGTGCGCCCGCGAGGAAACCAAGCGTGTCCCCCCCAGGACATTCCGCCCGGGTCCGCGTCCTACCGCATCAGCGATAGCAACTTTGTCCAATGTGGTTCCAACTGCACCATGATCATAGACGGAGACGTGGTGCGCGGGCGCCCCCAGGACCCGGGGGCCGCGGCATCCCCCGCTCCCTTCGTTGCGGTGACAAACATCGGAGCCGGCAGCGACGGCGGGACCGCCGTCGTGGCATTCGGGGGAACCCCACGTCGCTCGGCGGGGACGTCTACCGGTACCCAGACGACCGACGTCCCCACCGAGGCCCTTGGGGGCCCCCCTCCTCCTCCCCGCTTCACCCTGGGTGGCGGCTGTTGTTCCTGTCGCGACACACGGCGCCGCTCTGCGGTATTCGGGGGGGAGGGGGATCCCGTCGGCCCCGCGGAGTTCGTCTCGGACGACCGGTCGTCCGATTCCGACTCGGATGACTCGGAGGACACCGACTCGGAGACGCTGTCACACGCCTCCTCGGACGTGTCCGGCGGGGCCACGTACGACGACGCCCTTGACTCCGATTCGTCATCGGATGACTCCCTGCAGATAGATGGCCCCGTGTGTCGCCCGTGGAGCAATGACACCGCGCCCCTGGATGTTTGCCCCGGGACCCCCGGCCCGGGCGCCGACGCCGGTGGTCCCTCAGCGGTAGACCCACACGCCCGACGCCAGGGGCCGGCGCTGGTCTTGCGGCCGATCCCGCCGTGGCCCGGGACGACGCGGAGGGGCTTTCGGACCCCCGGCCACGTCTGGGAACGGGCACGGCCTACCCCGTCCCCCTGGAACTCACGCCCGAGAACGCGGAGGCCGTGGCGCGCTTTCTGGGAGATGCCGTGAACCGCGAACCCGCGCTCATGCTGGAGTACTTTTGCCGGTGCGCCCGCGAGGAAACCAAGCGTGTCCCCCCCAGGACATTCTGCAGCCCCCCTCGCCTCACGGAGGACGACTTTGGGCTTCTCAACTACGCGCTCGTGGAGATGCAGCGCCTGTGTCTGGACGTTCCTCCGGTCCCGCCGAACGCATACATGCCCTATTATCTCAGGGAGTATGTGACGCGGCTGGTCAACGGGTTCAAGCCGCTGGTGAGCCGGTCCGCTCGCCTTTACCGCATCCTGGGGGTTCTGGTGCACCTGCGGATCCGGACCCGGGAGGCCTCCTTTGAGGAGTGGCTGCGATCCAAGGAAGTGGCCCTGGACTTTGGCCTGACGGAAAGGCTTCGCGAGCACGAAGCCCAGCTGGTGATCCTGGCCCAGGCTCTGGACCATTACGACTGTCTGATCCACAGCACACCGCACACGCTGGTCGAGCGGGGGCTGCAATCGGCCCTGAAGTATGAGGAGTTTTACCTAAAGCGCTTTGGCGGGCACTACATGGAGTCCGTCTTCCAGATGTACACCCGCATCGCCGGCTTTTTGGCCTGCCGGGCCACGCGCGGCATGCGCCACATCGCCCTGGGGCGAGAGGGGTCGTGGTGGGAAATGTTCAAGTTCTTTTTCCACCGCCTCTACGACCACCAGATCGTACCGTCGACCCCCGCCATGCTGAACCTGGGGACCCGCAACTACTACACCTCCAGCTGCTACCTGGTAAACCCCCAGGCCACCACAAACAAGGCGACCCTGCGGGCCATCACCAGCAACATCAGCGCCATCCTCGCCCGCAACGGGGGCATCGGGCTATGCGTGCAGGCGTTTAACGACTCCGGCCCCGGGACCGCTAGCGTCATACCCGCCCTCAAGGTCCTCGACTCGCTGGTGGCGGCGCACAACAAAGGAGCGCGCGTCCAACCGGCGCGTGCGTGTACCTGGAGCCGTGGCACACCGACGTGCGGGCCGTGCTCCGGATGAAGGGGGTCCTCGCCGGCGAAGAGGCCCAGCGCTGCGACAATATCTTCAGCGCCCTCTGGATGCCAGACCTGTTTTTCAAGCGCCTGATTCGCCACCTGGACGGCGAGAAGAACGTCACATGGACCCTGTTCGACCGGGACACCAGCATGTCGCTCGCCGACTTTCACGGGGAGGAGTTCGAGAAGCTCTACCAGCACCTCGAGGTCATGGGGTTCGGCGAGCAGATACCCATCCAGGAGCTGGCCTATGGCATTGTGCGCAGTGCGGCCACGACCGGGAGCCCCTTCGTCATGTTCAAAGACGCGGTGAACCGCCACTACATCTACGACACCCAGGGGGCGGCCATCGCCGGCTCCAACCTCTGCACCGAGATCGTCCATCCGGCCTCCAAGCGATCCAGTGGGGTCTGCAATCTGGGAAGCGTGAATCTGGCCCGATGCGTCTCCAGGCAGACGTTTGACTTTGGGCGGCTCCGCGACGCCGTGCAGGCGTGCGTGCTGATGGTGAACATCATGATCGACAGCACGCTACAACCCACGCCCCAGTGCACCCGCGGCAACGACAACCTGCGGTCCATGGGAATCGGCATGCAGGGCCTGCACACGGCCTGCCTGAAGCTGGGGCTGGATCTGGAGTCTGTCGAATTTCAGGACCTGAACAAACACATCGCCGAGGGATGCTGCTGTCGGCGATGAAGACCAGCAACGCGCTGTGCGTTCGCGGGGCCCGTCCCTTCAACCACTTTAAGCGCAGCATGTATCGCGCCGGCCGCTTTCACTGGGAGCGCTTTCCGGACGCCCGGCCGCGGTACGAGGGCGAGTGGGAGATGCTACGCCAGAGCTGGATGAAACACGGCCTGCGCAACAGCCAGTTTGTCGCGCTGATGCCCACCGCCGCCTCGGCGCAGATCTCGGACGTCAGCGAGGGCTTTGCCCCCCTGTTCACCAACCTGTTCAGCAAGGTGACCCGGGACGGCGAGACGCTGCGCCCCAACACGCTCCTGCTAAAGGAACTGGAACGCACGTTTAGCGGGAAGCGCCTCCTGGAGGTGATGGACAGTCTCGACGCCAAGCAGTGGTCCGTGGCGCAGGCGCTCCCGTGCCTGGAGCCCACCCACCCCCTCCGGCGATTCAAGACCGCGTTTGACTACGACCAGAAGTTGCTGATCGACCTGGTGCGGACCGCGCCCCCTACGTCGACCATAGCCAATCCATGACCCTGTATGTCACGGAGAAGGCGGACGGGACCCTCCCAGCCTCCACCCTGGTCCGCCTTCTGGTCCACGCATATAAGCGCGGACTAAAAACAGGGATGTACTACTGCAAGGTTCGCAAGGCGACCAACAGCGGGGTCTTTGGCGGCGACGACAACATTGTCTGCACGAGCTGCGCGCTGTGACCGACAAACCCCCTCCGCGCCAGGCCCGCCGCCACTGTCGTCGCCGTCCCACGCGCTCCCCCGCTGCCATGGATTCCGCGGCCCCAGCCCTCTCCCCCGCTCTGACGGCCCATACGGGCCAGAGCGCGCCGGCGGACCTGGCGATCCAGATTCCAAAGTGCCCCGACCCCGAGAGGTACTTCTACACCTCCCAGTGTCCCGACATTAACCACCTGCGCTCCCTCAACATCCTTAACCGCTGGCTGGAAACCGAGCTTGTTTTCGTGGGGGACGAGGAGGACGTCTCCAAGCTTTCCGAGGGCGAGCTCAGCTTTTACCGCTTCCTCTTCGCTTTCCTGTCGGCCGCCGACGACCTGGTTACGGAAAACCTGGGCGGCCTCTCCGGCCTGTTTGAGCAGAAGGACATTCTCCACTACTACGTGGAGCAGGAATGCATCGAAGTCGTACACTCGCGCGTGTACAACATCATCCAGCTGGTGCTTTTTCACAACAACGACCAGGCGCGCCGCGAGTACGTGGCCGGCACCATCAACCACCCGGCCATCCGCGCCAAGGTGGACTGGCTGGAAGCGCGGGTGCGGGAATGCGCCTCCGTTCCGGAAAAGTTCATCCTCATGATCCTCATCGAGGGCATCTTTTTTGCCGCCTCGTTTGCCGCCATCGCCTACCTTCGCACCAACAACCTTCTGCGGGTCACCTGCCAGTCAAACGACCTCATCAGCCGGGACGAGGCCGTGCACACGACGGCCTCGTGTTACATCTACAACAACTACCTCGGCGGGCACGCCAAGCCCCCGCCCGACCGCGTGTACGGGCTGTTCCGCCAGGCGGTCGAGATCGAGATCGGATTTATCCGATCCCAGGCGCCGACGGACAGCCATATCCTGAGCCCGGCGGCGCTGGCGGCCATCGAAAACTACGTGCGATTCAGCGCGGATCGCCTGTTGGGCCTTATCCACATGAAGCCACTGTTTTCCGCCCCACCCCCCGACGCCGTATGTCCCGGAGAAGGCGGACGGGACCCTCCCAGCCTCCCCCTGGTCCGCCTTCTGGTCCACGCATATAAGCGCGGACTAAAAACAGGGATGTACTACTGCAAGGTTCGCAAGGCGACCAACAGCGGGGTCTTTGGCGGCGACGACAACATTGTCTGCACGAGCTGCGCGCTGTGACCGACAAACCCCCCCGCGCCAGGCCCGCCGCCACTGTCGTCGCCGTCCCACGCGCTCCCCCGCTGCCATGGATTCCGCGGCCCCAGCCCCCCCCCGCTCGACGGCCCATACGGGCCAGAGCGCGCCGGCGGACCTGGCGATCCAGATTCCAAAGTGCCCCGACCCCGAGAGGTACTTCTACACCTCCCAGTGTCCCGACATTAACCACCTGCGCTCCCTCAACATCCTTAACCGCTGGCTGGAAACCGAGCTTGTTTTCGTGGGGGACGAGGAGGACGTCTCCAAGCTTTCCGAGGGCGAGCTCAGCTTTTACCGCTTCCTCTTCGCTTTCCTGTCGGCCGCCGACGACCTGGTTACGGAAAACCTGGGCGGCCTCTCCGGCCTGTTTGAGCAGAAGGACATTCTCCACTACTACGTGGAGCAGGAATGCATCGAAGTCGTACACTCGCGCGTGTACAACATCATCCAGCTGGTGCTTTTTCACAACAACGCCAGGCGCGCCGCGAGTACGTGGCCGGCACCATCAACCACCCGGCCATCCGCGCCAAGGTGGACTGGCTGGAAGCGCGGGTGCGGGAATGCGCCTCCGTTCCGGAAAAGTTCATCCTCATGATCCTCATCGAGGGCATCTTTTTTGCCGCCTCGTTTGCCGCCATCGCCTACCTTCGCACCAACAACCTTCTGCGGGTCACCTGCCAGTCAAACGACCTCATCAGCCGGGACGAGGCCGTGCACACGACGGCCTCGTGTTACATCTACAACAACTACCTCGGCGGGCACAACCTTCTGCGGGTCACCTGCCAGTCAAACGACCTCATCAGCCGGGACGAGGCCGTGCACACGCGGCCTCGTGTTACATCTACAACAACTACCTCGGCGGGCACGCCAAGCCCCCGCCCGACCGCGTGTACGGGCTGTTCCGCCAGGCGGTCGAGATCGAGATCGGATTTATCCGATCCCAGGCGCCGACGGACAGCCATATCCTGAGCCCGGCGGCGCTGGCGGCCATCGAAAACTACGTGCGATTCAGCGCGGATCGCCTGTTGGGCCTTATCCACATGAAGCCACTGTTTTCCGCCCCACCCCCCGACGCCAGCTTTCCGCTGAGCCTCATGTCCACCGACAAACACACCAATTTTTTCGAGTGTCGCAGCACCTCCTACGCCGGGGCGGTCGTCAACGATCTGTGAGGGTCGCGGCGCGCTTCTACCCGTGTTTGCCCATAATAAACCTCTGAACCAAACTTTGGGTCTCATTGTGATTCTTGTCAGGGACGCGGGGGTGGGAGAGGATAAAAGGCGGCGCAAAAAGCAGTAACCAGGTCCGTCCAGATTCTGAGGGCATAGGATACCATAATTTTATTGGTGGGTCGTTTGTTCGGGGACAAGCGCGCTCGTCTGACGTTTGGGCTACTCGTCCCAGAATTTGGCCAGGACGTCCTTGTAGAACGCGGGTGGGGGGGCCTGGGTCCGCAGCTGCTCCAGAAACCTGTCGGCGATATCAGGGGCCGTGATATGCCGGGTCACAATAGATCGCGCCAGGTTTTCGTCGCGGATGTCCTGGTAGATAGGCAGGCGTTTCAGAAGAGTCCACGGCCCCCGCTCCTTGGGGCCGATAAGCGATATGACGTACTTAATGTAGCGGTGTTCCACCAGCTCGGTGATGGTCATGGGATCGGGGAGCCAGTCCAGGGACTCTGGGGCGTCGTGGATGACGTGGCGTCGCCGGCTGGCCACATAACTGCGGTGCTCTTCCAGCAGCTGCGCGTTCGGGACCTGGACGAGCTCGGGCGGGGTGAGTATCTCCGAGGAGGACGACCTGGGGCCGGGGTGGCCCCCGGTAACGTCCCGGGGATCCAGGGGGAGGTCCTCGTCGTCTTCGTATCCGCCGGCGATCTGTTGGGTTAGAATTTCGGTCCACGAGACGCGCATCTCGGTGCCGCCGGCGGCCGGCGGCAAAGGGGGCCTGGTTTCCGTGGAGCGCGAGCTGGTGTGTTCCCGGCGGATGGCCCGCCGGGTCTGAGAGCGACTCGGGGGGGTCCAGTGACATTCGCGCAGCACATCCTCCACGGAGGCGTAGGTGTTATTGGGATGGAGGTCGGTGTGGCAGCGGACAAAGAGGGCCAGGAACTGGGGGTAGCTCATCTTAAAGTACTTTAGTATATCGCGACTTGATCGTGGGAATGTAGCAGGCGCTAATATCCAACACAATATCACAGCCCATCAACAGGAGGTCAGTGTCTGTGGTGTACACGTACGCGACCGTGTTGGTGTGATAGAGGTTGGCGCAGGCATCGTCCGCCTCCAGCTGACCCGAGCTAATGTAGGGACCCCAGGGCCCGGAGAACGCGAATACAGAACAGATGCGCCAGACGCAGGGCCGGCTTCGAGGGCGCGGCGGACGGCAGCGCGGCTCCGGCCCGGCCGTCCCCCGGGTCCCCGAGGCCAGAGAGGTGCCGCGCCGGCGCATGTTGGAAAAGGCAGAGCTGGGTCTGGAGTCGGTGATGGGGGAAGGCGGTGGAGAGGCGTCCACGTCACTGGCCTCCTCGTCCGTCCGGCATTGGGCCGTCGTGCGGGCCAGGATGGCCTTGGCTCCAAACACAACCGGCTCCATACAATTGACCCCGCGATCGGTAACGAAGATGGGGAAAAGGGACTTTTGGGTAAACACCTTTAATAAGCGACAGAGGCAGTGTAGCGTAATGGCCTCGCGGTCGTAACTGGGGTAGCGGCGCTGATATTTGACCACCAACGTGTACATGACGTTCCACAGGTCCACGGCGATGGGGGTGAAGTACCCGGCCGGGGCCCCAAGGCCCTGGCGCTTGACCAGATGGTGTGTGTGGGCAAACTTCATCATCCCGAACAAACCCATGTCAGGTCGATTGTAACTGCGGATCGGCCTAACTAAGGCGTGGTTGGTGCGACGGTCCGGGACACCCGAGCCTGTCTCTCTGTGTATGGTGACCCAGACAACAACACCGACACAAGAGGACAATAATCCGTTAGGGGACGCTCTTTATAATTTCGATGGCCCAACTCCACGCGGATTGGTGCAGCACCCTGCATGCGCCGGTGTGGGCCAAACTTCCCCCCGCTCATTGCCTCTTCCAAAAGGGTGTGGCCTAACGAGCTGGGGGCGTATTTAATCAGGCTAGCGCGGCGGGCCTGCCGTAGTTTCTGGCTCGGTGAGCGACGGTCCGGTTGCTTGGGTCCCCTGGCTGCCAGCAAAACCCCACCCTCGCAGCGGCATACGCCCCCTCCGCGTCCCGCACCCGAGACCCCGGCCCGGCTGCCCTCACCACCGAAGCCCACCTCGTCACTGTGGGGTGTTCCCAGCCCGCATTGGGATGACGGATTCCCCTGGCGGTGTGGCCCCCGCCTCCCCCGTGGAGGACGCGTCGGACGCGTCCCTCGGGCAGCCGGAGGAGGGGGCGCCCTGCCAGGTGGTCCTGCAGGGCGCCGAACTTAATGGAATCCTACAGGCGTTTGCCCCGCTGCGCACGAGCCTTCTGGACTCGCTTCTGGTTATGGGCGACCGGGGCATCCTTATCCATAACACGATCTTTGGGGAGCAGGTGTTCCTGCCCCTGGAACACTCGCAATTCAGTCGGTATCGCTGGCGCGGACCCACGGCGGCGTTCCTGTCTCTCGTGGACCAGAAGCGCTCCCTCCTGAGCGTGTTTCGCGCCAACCAGTACCCGGACCTACGTCGGGTGGAGTTGGCGATCACGGGCCAGGCCCCGTTTCGCACGCTGGTTCAGCGCATATGGACGACGACGTCCGACGGCGAGGCCGTTGAGCTAGCCAGCGAGACGCTGATGAAGCGCGAACTGACGAGCTTTGTGGTGCTGGTTCCCCAGGGAACCCCCGACGTTCAGTTGCGCCTGACGAGGCCGCAGCTCACCAAGGTCCTTAACGCGACCGGGGCCGATAGTGCCACGCCCACCACGTTCGAGCTCGGGGTTAACGGCAAATTTTCCGTGTTCACCACGAGTACCTGCGTCACATTTGCTGCCCGCGAGGAGGGCGTGTCGTCCAGCACCAGCACCCAGGTCCAGATCCTGTCCAACGCGCTCACCAAGGCGGGCCAGGCGGCCGCCAACGCCAAGACGGTGTACGGGGAAAATACCCATCGCACCTTCTCTGTGGCGTCGACGATTGCAGCAGCGGGCGGTGCTCCGGCGACTGCAGGTCGCCGGGGGCACCCTCAAGTTCTTCCTCACGACCCCCGTCCCCAGTCTGTGCGTCACCGCCACCGGTCCCAACGCGGTATCGGCGGTATTTCTCCTGAAACCCCAGAAGATTTGCCTGGACTGGCTGGGTCATAGCCAGGGGTCTCCTTCAGCCGGGAGCTCGGCCTCCCGGGCCTCTGGGAGCGAGCCAACAGACAGCCAGGACTCCGCGTCGGACGCGGTCAGCCACGGCGATCCGGAAGACCTCGATGGCGCTGCCCGGGCGGGAGAGGCGGGGGCCTCGCACGCCTGTCCGATGCCGTCGTCGACCACGCGGGTCACTCCCACGACCAAGCGGGGGCGCTCGGGGGGCGAGGATGCGCGCGCGGACACGGCCCTAAAGAAACCTAAGACGGGGTCGCCCACCGCACCCCCGCCCACAGATCCAGTCCCCCTGGACACGGAGGACGACTCCGATGCGGCGGACGGGACGGCGGCCCGTCCCGCCGCTCCAGACGCCCGGAGCGGAAGCCGTTACGCGTGTTACTTTCGCGACCTCCCGACCGGAGAAGCAAGCCCCGGCGCCTTCTCCGCCTTCCGGGGGGGCCCCCAAACCCCGTATGGTTTTGGATTCCCCTGACGGGGCGGGGCCTTGGCGGCCGCCCAACTCTCGCACCATCCCGGGGTAATGTAAATAAACTTGGTATTGCCCAACACTCTCCCGCGTGTCGCGTGTGGTTCATGTGTGTGCCTGGCGTCCCCCACCCTCGGGGTCGTGTATTTCCTTTCCCTGTCCTTATAAAAGCCGTATGTGGGGCGCTGACGGAACCACCCCGCGTGCCATCACGGCCAAGGCGCGGGATGCTCCGCAACGACAGCCACCGGGCCGCGTCCCCGGAGGACGGCCAGGGACGGGTCGACGACGGACGGCCACACCTCGCGTGCGTGGGGGCCCTGGCGCGGGGGTTCATGCATATCTGGCTTCAGGCCGCCACGCTGGGTTTTGCGGGATCGGTCGTTATGTCGCGCGGGCCGTACGCGATGCCGCGTCTGGGGCGTTCGCCGTCGGGGCGCCGTGCTGGGCTTTATGCGCGCACCCCCCCCCTCGCGCGGCCCACCGCGCGGATATACGCCTGGCTCAAACTGGCGGCCGGTGGAGCGGCCCTTGTTCTGTGGAGTCTCGGGGAGCCCGGAACGCAGCCGGGGGCCCCGGGCCCGGCCACCCAGTGCCTGGCGCTGGGCGCCGCCTATGCGGCGCTCCTGGTGCTCGCCGATGACGTCTATCCGCTCTTTCTCCTCGCCCCGGGGCCCCTGTTCGTCGGCACCCTGGGGATGGTCGTCGGCGGGCTGACGATCGGAGGCAGCGCGCGCTACTGGTGGATCGGTGGGCCCGCCGCGGCCGCCTTGGCCGCGGCGGTGTTGGCGGGCCCGGGGGCGACCACCGCCAGGGCTGCTTCTCCAGGGCGTGCCCCGACCACCGCCGCGTCTGCGTCATCGTCGCAGGCGAGTCTGTTTCCCGCCGCCCCCCGGAGGACCCAGAGCGACCCGGGGACCCCGGGCCACCGTCCCCCCCGACACCCCAACGATCCCAGGGGCCGCCGGCCGATGAGGTCGCACCGGCCGGGGTAGCGCGGCCCGAAAACGTCTGGGTGCCCGTGGTCACCTTTCTGGGGGCGGGCGCGCTCGCCGTCAAGACGGTGCGAGAACATGCCCGGGAAACGCCGGGCCCGGGCCTGCCGCTGTGGCCCCAGGTGTTTCTCGGAGGCCATGTGGCGGTGGCCCTGACGGAGCTGTGTCAGGCGCTTATGCCCTGGGACCTTACGGACCCGCTGCTGTTTGTTCACGCCGGACTGCAGGTCATCAACCTCGGGTTGGTGTTTCGGTTTTCCGAGGTTGTCGTGTATGCGGCGCTAGGGGGTGCCGTGTGGATTTCGTTGGCGCAGGTGCTGGGGCTCCGGCGTCGCCTGCACAGGAAGGACCCCGGGGACGGGGCCCGGTTGGCGGCGACGCTTCGGGGCCTCTTCTTCTCCGTGTACGCGCTGGGGTTTGGGGTGGGGGCGCTGCTGTGCCCTCCGGGGTCAACGGGCGGGTGGTCGGGCGATTGATATATTTTTCAATAAAAGGCATTAGTCCGAAACCGCCGGTGTGTGATGATTTCGCCATAACACCCAAACCCCGGATGGGGCCCGGGAAAATTCCGGAAGGGGACACGGGCTACCCTCACTACCGAGGGCGCTTGGTCGGGAGGCCGCATCGAACGCACACCCCCATCCGGTGGTCCGTGTGGAGGTCGTTTTTCAGTGCCCGGTCTCGCTTTGCCGGGAACGCTAGCCGATCCCTCGCGAGGGGGAGGCGTCGGGCATGGCCCCGGGGCGGGTGGGCCTTGCCGTGGTCCTGTGGAGCCTGTTGTGGCTCGGGGCGGGGGTGGCCGGGGGCTCGGAAACTGCCTCCACCGGGCCCACGATCACCGCGGGAGCGGTGACAAACGCGAGCGAGGCCCCCACATCGGGGTCCCCCGGGTCAGCCGCCAGCCCGGAAGTCACCCCCACATCGACCCCAAACCCCAACAATGTCACACAAAACAAAACCACCCCCACCGAGCCGGCCAGCCCCCCAACAACCCCCAAGCCCACCTCCACGCCCAAAAGCCCCCCCACGCCCCCCCCCGACCCCAAACCCAAGAACAACACCCCCCCCGCCAAGTCGGGCCGCCCCACTAAACCCCCCGGGCCCGTGTGGTGCGACCGCCGCGACCCATTGGCCCGGTACGGCTCGCGGGTGCAGATCCGATGCCGGTTTCGGAATTCCACCCGCATGGAGTTCCGCCTCCAGATATGGCGTTACTCCATGGGTCCGTCCCCCCCAATCGCTCCGGCTCCCGACCAGAGGAGGTCCTGACGAACATCCCGCCCCACCCGGGGGACTCCTGGTGTACGACAGCGCCCCCAACCTGACGGACCCCCACGTGTCTGGGCGGAGGGGGCCGGCCCGGGCGCCGACCCTCCGTTGTATTCGTCCCGGGCCGCTGCCGACCCAGCGGCTGATTATCGGCGAGGTGACGCCCGCGACCCAGGGAATGTATTACTTGGCCTGGGGCCGGATGGACAGCCCGCACGAGTACGGGACGTGGGTGCGCGTCCGCATGTTCCGCCCCCCGTCTCTGACCCTCCAGCCCCACGCGGTGATGGAGGGTCAGCCGTTCAAGGCGACGTGCACGGCCGCCGCCTACTACCCGCGTAACCCCGTGGAGTTTGTCTGGTTCGAGGACGACCGCCAGGTGTTTAACCCGGGCCAGATCGACACGCAGACGCACGAGCACCCCGACGGGTTCACCACAGTCTCTACCGTGACCTCCGAGGCTGTCGGCGGCCAGGTCCCCCCGCGGACCTTCACCTGCCAGATGACGTGGCACCGCGACTCCGTGATGTTCTCGCGACGCAATGCCACCGGGCTGGCCCTGGTGCTGCCGCGGCCAACCATCACCATGGAATTTGGGGTCCGGCATGTGGTCTGCACGGCCGGCTGCGTCCCCGAGGGCAAAAGAGGGAGTGACGTTGCCTGGTTCCTGGGGGACGACCCCTCACCGGCGGCTAAGTCGGCCGTTACGGCCCAGGAGTCGTGCGACCACCCCGGGCTGGCTACGGTCCGGTCCACCCTGCCCATTTCGTACGACTACAGCGAGTACATCTGTCGGTTGACCGGATATCCGGCCGGGATTCCCGTCTAGAGCACCACGGCAGTCACCAGCCCCCACCCAGGGACCCCACCGAGCGGCAGGTGATCGAGGCGATCGAGTGGGTGGGGATTGGAATCGGGGTTCTCGCGGCGGGGGTCCCGGTCGTAACGGCAATCGTGTACGTCGTCCGCACATCACAGTCGCGGCAGCGTCATCGGCGGTAACGCGAGACCCCCCCGTTACCTTTTTAATATCTATATAGTTTGGTCCCCCTCTATCCCGCCCACCGCTGGGCGCTATAAAGCCGCCACCCTCTCTTCCCTCAGGTCATCCTTGGTCGATCCCGAACGACACACGGCGTGGAGCAAAACGCCTCCCCCTGAGCCGCTTTCCTACCAACACAACGGCATGCCTCTGCGGGCATCGGAACACGCCTACCGGCCCCTGGGCCCCGGGACACCCCCCATGCGGGCTCGGCTCCCCGCCGCGGCCTGGGTTGGCGTCGGGACCATCATCGGGGGAGTTGTGATCATTGCCGCGTTGGTCCTCGTGCCCTCGCGGGCCTCGTGGGCACTTTCCCCATGCGACAGCGGATGGCACGAGTTCAACCTCGGGTGCATATCCTGGGATCCGACCCCCATGGAGCACGAGCAGGCGGTCGGCGGCTGTAGCGCCCCGGCGACCCTGATCCCCCGCGCGGCTGCCAAACAGCTGGCCGCCGTCGCACGCGTCCAGTCGGCAAGATCCTCGGGCTACTGGTGGGTGAGCGGAGACGGCATTCGGGCCTGCCTGCGGCTCGTCGACGGCGTCGGCGGTATTGACCAGTTTTGCGAGGAGCCCGCCCTTCGCATATGCTACTATCCCCGCAGTCCCGGGGGCTTTGTTCAGTTTGTAACTTCGACCCGCAACGCGCTGGGGCTGCCGTGAGGCGCGTGTACTGCGGTCTGTCTCGTCTCCTCTTCTCCCCTTCCCTCCCCCTCCGCATCCCAGGATCACACCGGCCAACGAGGGTTGGGGGGGGGTCCGGCACGGACCCAAAATAATAAACACACAATCACGTGCGATAAAAAGAACACGCGGTCCCCTGTGGTGTTTTTGGTTATTTTTATTAAATCTCGTCGACAAACAGGGGGAAAGGGGCGTGGTCTAGCGACGGCAGCACGGGCGGAGGCGTTCACCGGCTCCGGCGTCCTTCGCGTTTAAGCTTGGTCAGGAGGGCGCTCAGGGCGGCGACGTTGGTCGGGCCGTCGTTGGTCAGGGCGTTGGCTCGATGGCGGGCGAGGACGGGCGAGGGGCTCAACGGCGGGGGCGGGGGTCCGGTGCGGCCCGGGGGGGAAAATAGGGCGGATCCCCCCCAGTCGTACAGGGGGTTTTCCGCCTCAATGTACGGGGAGGCCGGCGCTGCATTCGCCGTGTTCACGCAGACGTTTTCGTAGACCCGCATCCATGGTATTTCCTCGTAGACACGCCCCCCGTCCTCGCTCCCCGCCGTATATTGACTCGTCGTCCTCGTAGGGGGCGTGCCGTTCGCGGGCCGAGGCGGCGTGGGTGGCTTTGCGGCGGGCGTCGTCGTCGTCGTCGTCGGCCGTCAGATACGTGGCTTCCATCTGGTCGGGTTCTCCCTCCGGGGCGGGTCCCCACACCCGTGGCCGATCGAGGCTCCCCAGAGACGCGCGCCGGACAAGAAGGGGGCACGTCGCCGCCGGCGGTCGCCTGTCGGGTCCCGCGACGTTACGGGCCGGGAGGCGCGGGGGCACCCCCCCCATGTGCGTGTAATACGTGGCCGGCTGTGCGGCCGCAGCGGGGGGCTCGGCGACCGGGTCGTCCGCATCCGGAAGCGGGGGCCCCGCGCCGTCCGCACGGCGCCTCCGGAACCGCCGGGTGGACGGCGCGGGGGTCGAGTGTAGGCGAGGTCGGGGGAGGGGCGGGGGCTCGTTGTCGCGCCGCGCCCGCTGAATCTTTTCCCGACAGGTCCCACCCCCCGCGCGATGCCCCCCCGGGCCGCGGGCCATGTCGTCCGGGGGAGGCCCCGCGGACCACGTCGTCCGGCGAGACGCCACGAGCCGCAGGATGGACTCGTAGTGGAGCGACGGCGCCCCGCTGCGGAGCAGATCCGCGGCCAGGGCGGCCCCGAACCAAGCCTTGATGCTCACTCCATCCGGGCCCAGCTGGGGGCGGTCATCGTGGGGAACAGGGGGGCGGTGGTCCGACAGAAACGCTCCTGGCTGTCCACCGCGGCCCGCAGATACTCGTTGTTCAGGCTGTCGGTGGCCCAGACGCCGTACCCGGTGAGGGTCGCGTTGATGATATACTGGGCGTGGTGATGGACGATCGACAGAACCTCCACCGTGGATACCACGGTATCCACGGTCCCGTACGTACCGCCGCTCCGCTTGCCGGTCTGCCACAGGTTGGCTAGGCACGTCAGGTGGCCCAGGACGTCGCTGACCGCCGCCCTGAGCGCCATGCACTGCATGGAGCCGGTCGTGCCGCTGGGACCCCGGTCCAGATGGCGCGCGAACGTTTCCGCGGGCGCCTCCGGGCTGCCGCCGAGCGGGAGGAACCGGCGATTGGAGGGACTCAGCCGGGACATACGTGCTTGTCCGTCGTCCACAGCATCCAGGACGCCCACCGGTACAGCACGGGGACGTAGGCCAGGAGCTCGTTGAGCCGCAGTGCGGTGTCGGTGCTGGGGCGGCTTGGGTCCGCCGGGCGCAAGAACATGTCGCTGATCCGATGGAGGGCGTCGCGCAGGCCGGCCACGGTGGCGGCGTACTTGGCCGCCGCGGCCCCGCTCTTGACGGGGTGCGCGCCAGCAGCTTTGGCGCCAGGGTGGGCCGCAGCAGCACGTGAAGGCTGGGGTCGCAGTCGCCCACGGGGTCCTCGGGGACGTCCAGGCCGCTGGGCACCACCGTCTGCAGGTACTTCCAGTACTGCGTGAGGATGGAGAGGAGAAAAGGGCCGCCGGGCAGCTCCACCTCGCCCAGCGCCTGGGTGGCGGCCGAAGCGTAGTGCCGGATGTACCGTAGTGCGGGTCGCTGGCGAGCCCGTCCACGATCAAACTCTCGGGAACCGTGTTGTGTTGCCGCGCGGCCAACCGGACGCTGCGATCGGTGCAGGTCAGAAACGCCGGCTGCGCGTCGTCGGAGCGCTGCCGCAAGGCGCCCACGGCCGCGCTAAGGAGCCCCTCCGGGGTGGGGAGCAGACACCCGCCGAAGATGCGCCGCTCGGGAACGCCCGCGTTGTCGCCGCGGATCAGGTTGGCAGGCGTCAGGCACCGCGCCAGCCGCAGGGAGCTCGCGCCGCGCGTCCGGCGCTGCATGGTGACGCCCGTTCGGTCGGGACCCGCCGGTCGGAGTTATGCCGCGTCCAGGGCCATCGGGGCGCTTTTTATCGGGAGGAGCTTATGGGCGTGGCGGGCCTCCCAGCCCGGTCGCGCGCCTCCCCGACACGTGCGCCCGCAGGGCGGCGGCCCCCTCGTCTCCCATCAGCAGTTTCCTAAACTGGGACATGATGTCCACCACGCGGACCCGCGGGCCCAACACGGACCCGCCGCTTACGGGGGCGGGGGGGAAGGGCTCCAGGTCCTTGAGCAGAAAGGCGGGGTCTGCCGTCCCGGACACGGGGGCCCGGGGCGCGGAGGAGGCGGGGCGCAGATCCACGTGCTCCGCGGCCGCGCGGACGTCCGCCCAGAACTTGGCGGGGGTGGTGCGCGCGTACAGGGGCTGGGTCGCTCGGAGGACACACGCGTAGCGCAGGGGGGTGTACGTGCCCACCTCGGGGGCCGTGAATCCCCCGTCAAACGCGGCCAGTGTCACGCACGCCACCACGGTGTCGGCAAAGCCCAGCAGCCGCTGCAGGACGAGCCCGGCGGCCAGAATGGCGCGCGTGGTCGCAGCGTCGTCCCGGCGCCGGTGCGCGTCCCCGCACGCCCGGGCGTACTTTAAGGTCACTGTCGCCAGGGCCGTGTGCAGCGCGTACACCGCAGCGCCCAGCACGGCGTTGAGCCCGCTGTTGGCGAGCAGCCGGCGCGCTGCGGTGTCGCCCAGCGCCTCGTGCTCGGCCCCCACGACCGCGGGGCTTCCCAGGGGCAGGGCGCGAAACAGCTCCTCCCGCGCCACGTCCGCAAAGGCGGGGTGGTGCACGTGCGGGTGCAGGCGCGCCCCCACGACCACCGAGAGCCACTGGACCGTCTGCTCCGCCATCACCGCCAACACATCCAGCACGCGCCCCAGGAAGGCGGCCTCCCGCGTCAAAACGCACCGGACGGCGTCGGGATTGAAGCGGGCGAGCAGGGCCCCGGTGGCCAGGTACGTCATGCGGCCGGCATAGCGGGCGGCCACGCGACAGTCGCGGTCCAGCAGCGCGCGCACCCCGGGCCAGTACAGCAGGGACCCCAGCGAGCTGCGAAACACCGCGGCGTCGGGGCCGGATTGGGGGGACACTAACCCCCCCGCGCTCAGTAACGGCACGGCCGCGGCCCCGACGGGACGCCCGCCTCTCGCGAACTGCCGCCTCAGCTCGGCAGCCCTGTCGTCCAGGTCCGACCCGCGCGCCTCTGCGTGAAGGCGCGTCCCGCACACCCACCCGTTGATGGCCAGCCGCACGACGGCATCCGCCAAAAAGCTCATCGCCTGGGCGGGGCTGGTTTTTGTTCGACGATCCGTCAGGTCAAGAATCCCATCGCCCGTGATATACCAGGCCAACGCCTCGCCCTGCTGCAGGGTTTGGCGGAAAAACACCGCGGGGTTGTCGGGGGAGGCGAAGTGCATGACCCCCACGCGCGATAACCCGAACGCGCTATCCGGACACGGGTAAAACCCGGCCGGATGCCCCAGGGCTAGGGCGGAGCGCACGGACCGTCACACACGGCAACCTGAGGGGCCAGTCGATCCAACGGGAATGCCGCCCGGAGCTCCGGGCCCGGCCCGCGTCCCTCCAGACCCTCCCCTTGGGCGGGGAACGGGCCCCGCCGCCGTCCTCCGGCCCGACGTCTTCCGGGTAGTCGTCCTCCTCGTACTGCAGTTCCTCTAGGAACAGCGGCGACGGCGCCCCCCGCGAACCGCCGACCCGCCCCAAAATAGCCCGCGCGTCGACGGGACCCAGGTATCCCCCCTGCCGGGCCTGCGGAGGACCGCGGGGAACCTCATCATCATCGTCCAGGCGACCGCGCACCGACTGGCTACGGGCCGCATCGGGCCCGGGGCGCTGCCGGGACGCTCGGCGATGGGATGAGGGCGGGGCTTCCGACGCGCGCCGTCGTCGGGCTCGCGGGCCTTCCCGTCGACGGCGCACGGGCGGCTCGTCGCCCGCCATCTCCTCCAGAGCCTCTAGCTCGCTGTCGTCATCCCCGCGGAACACCGCACGCAGGTACCCCATGAACCCCCCCCATCGCCCGCTGGCTCGTCCGCCACGGGCGAGGCGCGGGGGCGGGTGGATGCGCGCCTCCTGCGCCCCGCGGGTTCGCGAGCCGACATGGTGGCGATAGACGCGGGTATCGGATGTCCGCTACCCCCCAAAAAAGAAAAAGACCCCACAGCGCGGATGGAGGTCGGGGTAGGTGCCGCCGGACCCCCTCGCGATGGGAATGGACGGGAGCGACGGGGCCGGCGCAAAAAACGCAGTATCTCCCGCGAAGGCTACCCGCCGCCCCAGCCCCCGGCCAAATGCGGAAACGGTCCCGCGCTCTCGCCTTTATACGCGGGCCGCCCTGCGACACAATCACCCGTCCGTGGTTTCGAATCTACACGACAGGCCCGCAGACGCGGCTAACACACACGCCGGCAACCCAGACCCCAGTGGGTTGGTTGCGCGGTCCCGTCTCCTGGCTAGTTCTTTCCCCCACCACCAAATAATCAGACGACAACCGCAGGTTTTTGTAATGTATGTGCTCGTGTTTATTGTGGATACGAACCGGGGACGGGAGGGGAAAACCCAGACGGGGGATGCGGGTCCGGTCGCGCCCCCTACCCACCGTACTCGTCAATTCCAAGGGCATCGGTAAACATCTGCTCAAACTCGAAGTCGGCCATATCCAGAGCGCCGTAGGGGGCGGAGTCGTGGGGGGTAAATCCCGGACCCGGGGAATCCCCGTCCCCCAACATGTCCAGATCGAAATCGTCTAGCGCGTCGGCATGCGCCATCGCCACGTCCTCGCCGTCTAAGTGGAGCTCGTCCCCCAGGCTGACATCGGTCGGGGGGGCCGTCGACAGTCTGCGCGTGTGTCCCGCGGGGAGAAAGGACAGGCGCGGAGCCGCCAGCCCCGCCTCTTCGGGGGCGTCGTCGTCCGGGAGATCGAGCAGGCCCTCGATGGAGACCCGTAATTGTTTTTCGTACGCGCGCGGCTGTACGCGTGTTCCCGCATGACCGCCTCGGAGGGCGAGGTCGTGAAGCTGGAATACGAGTCCAACTTCGCCCGAATCAACACCATAAAGTACCCAGAGGCGCGGGCCTGGTTGCCATGCAGGGTGGGAGGGGTCGTCAACGGCGCCCCTGGCTCCTCCGTAGCCGCGCTGCGCACCAGCGGGAGGTTAAGGTGCTCGCGAATGTGGTTTAGCTCCCGCAGCCGGCGGGCCTCGATTGGCACTCCCCGGACGGTGAGCGCTCCGTTGACGAACATGAAGGGCTGGAACAGACCCGCCAACTGACGCCAGCTCTCCAGGTCGCAACAGAGGCAGTCAAACAGGTCGGGCCGCATCATCTGCTCGGCGTACGCGGCCCATAGGATCTCGCGGGTCAAAAATAGATACAAATGCAAAAACAGAACACGCGCCAGACGAGCGGTCTCTCGGTAGTACCTGTCCGCGATCGTGGCGCGCAGCATTTCTCCCAGGTCGCGATCGCGTCCGCGCATGTGCGCCTGGCGGTGCAGCTGCCGGACGCTGGCGCGCAGGTACCGGTACAGGGCCGAGCAGAAGTTGGCCAACACGGTTCGATAGCTCTCCTCCCGCGCCCGTAGCTCGGCGTGGAAGAAACGAGAGAGCGCTTCGTAGTAGAGCCCGAGGCCGTCGCGGGTGGCCGGAAGCGTCGGGAAGGCCACGTCGCCGTGGGCGCGAATGTCGATTTGGGCGCGTTCGGGGACGTACGCGTCCCCCCATTCCACCACATCGCTGGGCAGCGTTGATAGGAATTTACACTCCCGGTACAGGTCGGCGTTGGTCGGTAACGCCGAAAACAAATCCTCGTTCCAGGTATCGAGCATGGTACATAGCGCGGGGCCCGCGCTAAAGCCCAAGTCGTCGAGGAGACGGTTAAAGAGGGCGGCGGGGGGGACGGGCATGGGCGGGGAGGGCATGAGCTGGGCCTGGCTCAGGCGCCCCGTTGCGTACAGCGGAGGGGCCGCCGGGGTGTTTTTGGGACCCCCGGCCGGGCGGGGGGGTGGTGGCGAAGCGCCGTCCGCGTCCATGTCGGCAAACAGCTCGTCGACCAAGAGGTCCATTGGGTGGGGTTGATACGGGAAAGACGATATCGGGCTTTTGATGCGATCGTCCCCGCCCGCCCCGCGAGTGTGGGACGCCCGACGGCGCGGGAAGAGAAAAACCCCCAAACGCGTTAGAGGACCGGACGGACCTTATGGGGGGAAGTGGGCAGCGGGAACCCCGTCCGTTCCCGAGGAATGACAGCCCGTGGTCGCCACCCCGCATTTAAGCAACCCGCACGGGCCGCCCCGTACCTCGTGACTTCCCCCCACATTGGCTCCTGTCACGTGAAGGCAAACCGAGGGCGGCTGTCCAACCCACCCCCCGCCACCCAGTCACGGTCCCCGTCGGATTGGGAAACAAAGGCACGCAACGCCAACACCGAATGAACCCCTGTTGGTGCTTTATTGTCTGGGTACGGAAGTTTTTCACTCGACGGGCCGTCTGGGGCGAGAAGCGGAGCGGGCTGGGGCTCGAGGTCGCTCGGTGGGGCGCGACGCCGCAGAACGCCCTCGAGTCGCCGTGGCCGCGTCGACGTCCTGCACCACGTCTGGATTCACCAACTCGTTGGCGCGCTGAATCAGGTTTTTGCCCTCGCAGACCGTCACGCGGATGGTGGTGATGCCAAGGAGTTCGTTGAGGTCTTCGTCTGTGCGCGGACGCGACATGTCCCAGAGCTGGACCGCCGCCATCCGGGCATGCATGGCCGCCAGGCGCCCAACCGCGGCGCAGAAGACGCGCTTGTTAAAGCCGGCCACCCGGGGGGTCCATGGCGCGTCGGGGTTTGGGGGGGCGGTGCTAAAGTGCAGCTTTCTGGCCAGCCCCTGCGCGGGTGTCTTGGATCGGGTTGGCGCCGTCGACGCGGGGGCGTCTGGGAGTGCGGCGGATTCTGGCTGGGCCGATTTCCTGCCGCGGGTGGTCTCCGCCGCCGGGGCCGCGGGGGCCTTAGTCGCCACCCGCTGGGTTCGGGGGGCCCGGGGGGCGGTGGTGGGTGGCGTCCGGCCCCTCCGGACCCAGCGGGCGGCGGGGGCGCCCGCGCAGGCCCCGGGGCGGACAAAACCGCCCCGGAAACGGGACGCCGCGTCCGGGGGACCTCCGGGTGTTCGTCGTCTTCGGATGACGAGCCCCCGTAGAGGGCATAATCCGACTCGTCGTACTGGACGAAACGGACCTCGCCCCTTGGGCGCGCGCGTGTCTGTAGGGCGCCACGGCGGGAGGTGTCAGGCGGACTATCGGGACTCGCCATACATGAAGACGGGGGTAGTACAGATCCTCGTACTCATCGCGCGGAACCTCCCGCGGACCCGACTTCACGGAGCGGCGAGAGGTCATGGTTCCACGAACACGCTAGGGTCGGATGCGCGGACAATTAGGCCTGGGTTCGGACGGCGGGGGTGGTGCAGGTGTGGAGAGGTCGAGCGATAGGGGCGGCCCGGGAGAGAAGAGAGGGTCCGCAAAACCCACTGGGGATGCGTGAGTGGCCCTCTGTGGGCGGTGGGGGAGAGTCTTATAGGAAGTGCATATAACCACAACCCATGGGTCTAACCAATCCCCAGGGGCCAAGAAACAGACACGCCCCAAACGGTCTCGGTTTCCGCGAGGAAGGGGAAGTCCTGGGACACCCTCCACCCCCACCCCTCACCCCACACAGGGCGGGTTCAGGCGTGCCCGGCAGCCAGTAGCCTCTGGCAGATCTGACAGACGTGTGCGATAATACACACGCCCATCGAGGCCATGCCTACATAAAAGGGCACCAGGGCCCCCGGGGCAGACATTTGGCCAGCGTTTTGGGTCTCGCACCGCGCGCCCCCGATCCCATCGCGCCCGCCCTCCTCGCCGGGCGGCTCCCCGTGCGGGCCCGCGTCTCCCGCCGCTAAGGCGACGAGCAAGACAAACAACAGGCCCGCCCGACAGACCCTTCTGGGGGGGCCCATCGTCCCTAACAGGAAGATGAGTCAGTGGGGATCCGGGGCGATCCTTGTCCAGCCGGACAGCTTGGGTCGGGGGTACGATGGCGACTGGCACACGGCCGTCGCTACTCGCGGGGGCGGAGTCGTGCAACTGAACCTGGTCAACAGGCGCGCGGTGGCTTTTATGCCGAAGGTCAGCGGGGACTCCGGATGGGCCGTCGGGCGCGTCTCTCTGGACCTGCGAATGGCTATGCCGGCTGACTTTTGTGCGATTATTCACGCCCCCGCGCTATCCAGCCCAGGGCACCACGTAATACTGGGTCTTATCGACTCGGGGTACCGCGGAACCGTTATGGCCGTGGTCGTAGCGCCTAAAAGGACGCGGGAATTTGCCCCCGGGACCCTGCGGGTCGACGTGACGTTCCTGGACATCCTGGCGACCCCCCCGGCCCTCACCGAGCCGATTTCCCTGCGGCAGTTCCCGCAACTGGCGCCCCCCCTCAACGGGGCCGGGATACGCGCAGATCCTTGGTTGGAGGGGGCGCTCGGGGACCCAAGCGTGACTCCTGCCCTACCGGCGCGACGCGAGGGCGGTCCCGCGCCCATGCCGGCGAGCTGACGCCGGTTCAGACGGAACACGGGGACGGCGTACGAGAAGCCATCGCCTTCCTTCCAAAACGCGAGGAGGATGCCGGTTTCGACATTGTCGTCCGTCGCCCGGTCACCGTCCCGGCAAACGGCACCACGGTCGTGCAGCCATCCCTCCGCATGCTCCACGCGGACGCCGGGCCCGCGGCCTGCTATGTGCTGGGGCGGTCGTCGCTCAACGCCCGCGGCCTCCTGGTCGTTCCTACGCGCTGGCTCCCCGGGCACGTATGTGCGTTTGTTGTTTACAACCTTACGGGGGTTCCTGTGACCCTCGAGGCCGGCGCCAAGGTCGCCCAGCTCCTGGTTGCGGGGGCGGACGCTCTTCCTTGGATCCCCCCGGACAACTTTCACGGGACCAAAGCGCTTCGAAACTACCCCAGGGGTGTTCCGGACTCAACCGCCGAACCCAGGAACCCGCCGCTCCTGGTGTTTACGAACGAGTTTGACGCGGAGGCCCCCCCGAGCGAGCGCGGGACCGGGGGTTTTGGCTCTACCGGTATTTAGCCCATAGCTTGGGGTTCGTTCCGGGCAATAAAAAACGTTTGTATCTCATCTTTCCTGTGTGTAGTTGTTTCTGTTGGATGCCTGTGGGTCTATCACACCCGCCCCTCCATCCCACAAACACAGAACACACGGGTTGGATGAAAACACGCATTTATTGACCCAAAACACACGGAGCTGCTCGAGATGGGCCAGGGCGAGGTGCGGTTGGGGAGGCTGTAGGTCTGGGAACGGACACGCGGGGACACGATTCCGGTTTGGGGTCCGGGAGGGCGTCGCCGTTTCGGGCGGCAGGCGCCAGCGTAACCCGGGGGCGGCGTGTGGGGGTGCCCCAAGGAGGGCGCCTCGGTCACCCCAAGCCCCCCCGAGCGGGTCCCCCGGCAACCCCGAAGGCGGAGAGGCCAAGGGCCCGGGCGGCGATGGCCACATCCTCCATGACCACGTCGCTCTCGGCCATGCTCCGAATAGCCTGGGAGACGAGCACATCCGCGGACTTGTCAGCCGCCCCCACGGACATGTACATCTGCAGGATGGTGGCCATACACGTGTCCGCCAGGCGCCGCATCTTGTCCTGATGGGCCGCCACGGCCCCGTCGATCGTGGGGGCCTCGAGCCCGGGGGGTGGCGCGCCAGTCGTTCTAGGTTCACCATGCAGGCGTGGTACGTGCGGGCCAAGGCGCGGGCCTTCACGAGGCGTCGGGTGTCGTCCAGGGACCCCAGGGCGTCATCGAGCGTGATGGGGGCGGGAGTAGCCCGCCCCTCCATCCCACAAACACAGAACACACGGGTTGGATGAAAACACGCATTTATTGACCCAAAACACACGGAGCTGCTCGAGATGGGCCAGGGCGAGGTGCGGTTGGGGAGGCTGTAGGTCTGGGAACGGACACGCGGGGACACGATTCCGGTTTGGGGTCCGGGAGGGCGTCGCCGTTTCGGGCGGCAGGCGCCAGCGTAACCTCCGGGGGCGGCGTGTGGGGGTGCCCCAAGGAGGGCGCCTCGGTCACCCCAAGCCCCCCCGAGCGGGTTCCCCCGGCAACCCCGAAGGCGGAGAGGCCAAGGGCCCGTTCGGCGATGGCCACATCCTCCATGACCACGTCGCTCTCGGCCATGCTCCGAATAGCCTGGGAGACGAGCACATCCGCGGACTTGTCAGCCGCCCCCACGGACATGTACATCTGCAGGATGGTGGCCATACACGTGTCCGCCAGGCGCCGCATCTTGTCCTGATGGGCCGCCACGGCCCCGTCGATCGTGGGGGCCTCGAGCCCGGGGTGGTGGCGCGCCAGTCGTTCTAGGTTCACCATGCAGGCGTGGTACGTGCGGGCCAAGGCGCGGGCCTTCACGAGGCGTCGGGTGTCGTCCAGGGACCCCAGGGCGTCATCGAGCGTGATGGGGGCGGGAAGTAGCGCGTTAACGACCACCAGGGCCTCCTGCAGCCGCGGCTCCGCCTCCGAGGGCGGACCGGCCGCGCGGATCATCTCATATTGTTCCTCGGGGCGCGCTCCCCAGCCACATATAGCCCCGAGAAGAAGCATCGCGGGCGGGTACGGCTTGGGCGCGCGGACGCAATGGGGCAGGAAGACGGGAACCGCGGGGAGAGGCGGGCGGCCGGGACTCCCGTGGAGGTGACCGCGCTTTATGCGACCGACGGGGGCGTTATTACCTCTTCGATCGCCCTCCTCACAAACTCTCTACTGGGGGCCGAGCCGGTTTATATATTCAGCTACGACGCATACACGCACGATGGCCGTGCCGACGGGCCCACGGAGCAAGACAGGTTCGAAGAGAGTAGGGCGCTCTACCAAGCGTCGGGCGGGCTAAATGGCGACTCCTTCCGAGTAACCTTTTGTTTATTGGGGACGGAAGTGGGTGGGACCCACCAGGCCCGCGGGCGAACCCGACCCATGTTCGTCTGTCGCTTCGAGCGAGCGGACGACGTCGCCGCGCTACAGGACGCCCTGGCGCACGGGACCCCGCTACAACCGGACCACATCGCCGCCACCCTGGACGCGGAGGCCACGTTCGCGCTGCATGCGAACATGACCTGGCTCTCACCGTGGCCGTCAACAACGCCAGCCCCCGCACCGGACGCGACGCCGCCGCGGCGCAGTATGATCAGGGCGCGTCCCTACGCTCGCTCGTGGGGCGCACGTCCCTGGGACAACGCGGCCTTACCACGCTATACGTCCACCACGAGGCGCGCGTGCTGGCCGCGTACCGCAGGGCGTATTATGGAAGCGCGCAGAGTCCCTTCTGGTTTCTTAGCAAATTCGGGCCTGACGAAAAAAGCCTGGTGCTCACCACTCGGTACTACCTGCTTCAGGCCCAGCGTCTGGGGGGCGCGGGGGCCACGTACGACCTGCAGGCCATCAAGGACATCTGCGCCACCTACGCGATTCCCCACGCCCCCCGCCCCGACACCGTCAGCGCCGCGTCCCTGACCTCGTTTGCCGCCATCCGCGGTTCTGTTGCACGAGCCAGTACGCCCGCGGGGCCGCGGCGGCCGGGTTTCCGCTTTACGTGGAGCGCCGTATTGCGGCCGACGTCCGCGAGACCAGTGCGCTGGAGAAGTTCATAACCCACGATCGCAGTTGCCTGCGCGTGTCCGACCGTGAATTCATTACGTACTTTCCCTGGCCCATTTTGAGTGTTTCAGCCCCCCGCGCCTAGCCACGCATCTTCGGGCCGTGACGACCCAGGACCCCAACCCCGCGGCCAACACGGAGCAGCCCTCGCCCCTGGGCAGGGAGGCCGTGGAACAATTTTTTTGCCACGTGCGCGCCCAACTGAATATCGGGGAGTACGTCAAACACAACGTGACCCCCCGGGAGACCGTCCTGGATGGCGATACGGCCAAGGCCTACCTGCGCGCTCGCACGTACGCGCCCGGGGCCCTGACGCCCGCCCCCGCGTATTGCGGGGCCGTGGACTCCGCCACCAAAATGAGGGGCGTTTGGCGGACGCCGAAAAGCTCCTGGTCCCCCGCGGGTGGCCCGCGTTTGCGCCCGCCAGTCCCGGGGAGGATACGGCGGAGGATACGGCGGGCGGCACGCCGCCCCCACAGCCTGCGGAATCGCAAGCGCCTCCTGAGACTGGCCGCCACGGAACAACAGGACACCACGCCCCCGGCGATCGCGGCGCTTATCCGTAATGCGGCGGTGCAGACTCCCCTGCCCGTCTACCGGATATCCATGGTCCCCACGGGACAGGCATTTGCCGCGCTGGCCTGGGACGACTGGGCCCGCATAACGCGGGACGCTCGCCTGGCCGAAGCGGTCGTGTCCGCCGAAGCGGCGGCGCACCCCGACCACGGCGCGCTGGGCAGGCGGCTCACGGATCGCATCCGCGCCCAGGGCCCCGTGATGCCCCCTGGCGGCCTGGATGCCGGGGGGCAGATGTACGTGAATCGCAACGAGATATTTAACGGCGCGCTGGCAATCACAAACATCATCCTGGATCTCGACATCGCCCTGAAGGAGCCCGTCCCCTTTCGCCGGCTCCACGAGGCCCTGGGCCACTTTAGGCGCGGGGCTCTGGCGGCGGTTCAGCTCCTGTTTCCCGCGGCCCGCGTGGCCCCGACGCATATCCCTGTTATTTTTTCAAAAGCGCATGTCGGCCCGGCCCGGCGTCCGTGGGTTCCGGCAGCGGACTCGGCAACGACGACGACGGGGACTGGTTTCCCTGCTACGACGCCGCCGGTGATGAGGAGTGGGCGGAGGACCCGGGCGCCATGGACACATCCCACGATCCCCCGGACGACGAGGTTGCCTACTTTGACCTGTGCCACGAAGTCGGCCCCACGGCGGAACCTCGCGAAACGGATTCGCCCGTGTGTTCCTGCACCGACAAGATCGGACTGCGGGTGTGCATGCCCGTCCCCGCCCCGTACGTCGTCCACGGTTCTCTACGATGCGGGGGGTGGCACGGGTCATCCAGCAGGCGGTGCTGTTGGACCGAGATTTTGTGGAGGCCATCGGGAGCTACGTAAAAACTTCCTGTTGATCGATACGGGGGTGTACGCCCACGGCCACAGCCTGCGCTTGCCGTATTTTGCCAAAATCGCCCCCGACGGGCCTGCGTGCGGAAGGCTGCTGCCAGTGTTTGTGATCCCCCCCGCCTGCAAAGACGTTCCGGCGTTTGTCGCCGCGCACGCCGACCCGCGGCGCTTCCATTTTCACGCCCCGCCCACCTATCTCGCTTCCCCCCGGGAGATCCGTGTCCTGCACAGCCTGGGTGGGGCTATGTGAGCTTCTTTGAAAGGAAGGCGTCCCACAACGCGCTGGAACACTTTGGGCGACGCGAGACCCTGACGGAGGTCCTGGGTCGGTACAACGTACAGCCGGATGCGGGGGGGACCGTCGAGGGGTTCGCATCGGAACTGCTGGGGCGGATAGTCGCGTGCATCGAAACCCACTTTCCCGAACACGCCGGCGAATATCAGGCCGTATCCGTCCGGCGGGCCGTCAGTAAGGACGACTGGGTCCTCCTACAGCTAGTCCCCGTTCGCGGTACCCTGCAGCAAAGCCTGTCGTGTCTGCGCTTTAAGCACGGCCGGGCGAGTCGCGCCACGGCGCGGACATTCGTCGCGCTGAGCGTCGGGGCCAACAACCGCCTGTGCGTGTCCTTGTGTCAGCAGTGCTTTGCCGCCAAATGCGACAGCAACCGCCTGCACACGCTGTTTACCATTGACGCCGGCACGCCATGCTCGCCGTCCGTTCCCTGCAGCACCTCTCAACCGTCGTCTTGATAACGGCGTACGGCCTCGTGCTCGTGTGGTACACCGTCTTCGGTGCCAGTCCGCTGCACCGATGTATTTCGTGGTACGCCCCACCGGCACCAACAACGACACCGCCCTCGTGTGGATGAAAATGAACCAGACCCTATTGTTTCTGGGGGCCCCGACGCACCCCCCCAACGGGGGCTGGCGCAACCACGCCCATATCTGCTACGCCAATCTTATCGCGGGTAGGGTCGTGCCCTTCCAGGTCCCACCCGACGCCACGAATCGTCGGATCATGAACGTCCACGAGGCAGTTAACTGTCTGGAGACCCTATGGTACACACGGGTGCGTCTGGTGGTCGTAGGGTGGTTCCTGTATCTGGCGTTCGTCGCCCTCCACCAACGCCGATGTATGTTTGGTGTCGTGAGTCCCGCCCACAAGATGGTGGCCCCGGCCACCTACCTCTTGAACTACGCAGGCCGCATCGTATCGAGCGTGTTCCTGCAGTCCCCCTACACGAAAATTACCCGCCTGCTCTGCGAGCTGTCGGTCCAGCGGCAAAACCTGGTTCAGTTGTTTGAGACGGACCCGGTCACCTTCTTGTACCACCGCCCCGCCATCGGGGTCATCGTAGGCTGCGAGTTGATGCTACGCTTTGTGGCCGTGGGTCTCATCGTCGGCACCGCTTTCATATCCCGGGGGGCATGTGCGATCACATACCCCCTGTTTCTGACCATCACCACCTGGTGTTTTGTCTCCACCATCGGCCTGACAGAGCTGTATTGTATTCTGCGGCGGGGCCCGGCCCCCAAGAACGCAGACAAGGCCGCCGCCCCGGGGCGATCCAAGGGGCTGTCGGGCGTCTGCGGGCGCTGTTGTTCCATCATCCTGTCGGGCATCGCAATGCGATTGTGTTATATCGCCGTGGTGGCCGGGGTGGTGCTCGTGGCGCTTCACTACGAGCAGGAGATCCAGAGGCGCCTGTTTGATGTATGACGTCACATCCAGGCCGGCGGAAACCGGAACGGCATATGCAAACTGGAAACTGTCCTGTCTTGGGGCCCACCCACCCGACGCGTCATATGTAAATGAAAATCGTTCCCCCGAGGCCATGTGTAGCCTGGATCCCAACGACCCCGCCCATGGGTCCCAATTGGCCGTCCCGTTACCAAGACCAACCCAGCCAGCGTATCCACCCCCGCCCGGGTCCCCGCGGAAGCGGAACGGTGTATGTGATATGCTAATTAAATACATGCCACGTACTTATGGTGTCTGATTGGTCCTTGTCTGTGCCGGAGGTGGGGCGGGGGCCCCGCCCGGGGGGCGGAACTAGGAGGGGTTTGGGAGAGCCGGCCCCGGCACCACGGGTATAAGGACATCCACCACCCGGCCGCCCCGCCCATGGGTCCCAATTGGCCGTCCCGTTACCAAGACCAACCCAGCCAGCGTATCCACCCCCGCCCGGGTCCCCGCGGAAGCGGAACGGTGTATGTGATATGCTAATTAAATACATGCCACGTACTTATGGTGTCTGATTGGTCCTTGTCTGTGCCGGAGGTGGGGCGGGGGCCCCGCCCGGGGGGCGGAACTAGGAGGGGTTTGGGAGAGCCGGCCCCGGCACCACGGGTATAAGGACATCCACCACCCGGCCGCTCCCTATCAGTGATAGAGATCTCCCTATCATGATAGAGATCGCTGCACTGAGGTGCAGGTACATCCAGCTGACGAGTCCCAAATAGGACGAAACGCGCTTCGGTGTGTCCTGGATTCCACTGCTATCCACCGGTGCGCCACCACCAGAGGCCATATCCGACACCCCAGCCCCGACGGCAGCCGACAGCCCGGTCATGGCGACTGACATTGATATGCTAATTGACCTCGGCCTGGACCTCTCCGACAGCGATCTGGACGAGGACCCCCCCGAGCCGGCGGAGAGCCGCCGCGACGACCTGGAATCGGACAGCAACGGGGAGTGTTCCTCGTCGGACGAGGACATGGAAGACCCCCACGGAGAGGACGGACCGGAGCCGATACTCGACGCCGCTCGCCCGGCGGTCCGCCCGTCTCGTCCAGAAGACCCCGGCGTACCCAGCACCCAGACGCCTCGTCCGACGGAGCGGCAGGGCCCCAACGATCCTCAACCAGCGCCCCACAGTGTGTGGTCGCGCCTCGGGGCCCGGCGACCGTCTTGCTCCCCCGAGCGGCACGGGGGCAAGGTGGCCCGCCTCCAACCCCCACCGACCAAAGCCCAGCCTGCCCGCGGCGGACGCCGTGGGCGTCGCAGGGGTCGGGGTCGCGGTGGTCCCGGGGCCGCCGATGGTTTGTCGGACCCCCGCCGGCGTGCCCCCAGAACCAATCGCAACCCGGGGGGACCCCGCCCCGGGGCGGGGTGGACGGACGGCCCCGGCGCCCCCCATGGCGAGGCGTGGCGCGGAAGTGAGCAGCCCGACCCACCCGGAGGCCCGCGGACACGGAGCGTGCGCCAAGCACCCCCCCCGCTAATGACGCTGGCGATTGCCCCCCCGCCCGCGGACCCCCGCGCCCCGGCCCCGGAGCGAAAGGCGCCCGCCGCCGACACCATCGACGCCACCACGCGGTTGGTCCTGCGCTCCATCTCCGAGCGCGCGGCGGTCGACCGCATCAGCGAGAGCTTCGGCCGCAGCGCACAGGTCATGCACGACCCCTTTGGGGGGCAGCCGTTTCCCGCCGCGAATAGCCCCTGGGCCCCGGTGCTGGCGGGCCAAGGAGGGCCCTTTGACGCCGAGACCAGACGGGTCTCCTGGGAAACCTTGGTCGCCCACGGCCCGAGCCTCTATCGCACTTTTGCCGGCAATCCTCGGGCCGCATCGACCGCCAAGGCCATGCGCGACTGCGTGCTGCGCCAAGAAAATTTCATCGAGGCGCTGGCCTCCGCCGACGAGACGCTGGCGTGGTGCAAGATGTGCATCCACCACAACCTGCCGCTGCGCCCCCAGGACCCCATTATCGGGACGGCCGCGGCGGTGCTGGATAACCTCGCCACCCGCCTGCGGCCCTTTCTCCAGTGCTACCTGAAGGCGCGAGGCCTGTGCGGCCTGGACGAACTGTGTTCGCGGCGGCGTCTGGCGGGCATTAAGGACATTGCATCCTTCGTGTTTGTCATTCTGGCCAGGCTCGCCAACCGCGTCGAGCGTGGCGTCGCGGAGATCGACTACGCGACCCTTGGTGTCGGGGTCGGAGAGAAGATGCATTTCTACCTCCCCGGGGCCTGCATGGCGGGCCTGATCGAAATCCTAGACACGCACCGCCAGGAGTGTTCGAGTCGTGTCTGCGAGTTGACGGCCAGTCACATCGTCGCCCCCCCGTACGTGCACGGCAAATATTTTTATTGCAACTCCCTGTTTTAGGTACAATAAAAACAAAACATTTCAAACAAATCGCCCCACGTGTTGTCCTTCTTTGCTCATGGCCGGCGGGGCGTGGGTCACGGCAGATGGCGGGGGTGGGCCCGGCGTACGGCCTGGGTGGGCGGAGGGAACTAACCCAACGTATAAATCCGTCCCCGCTCCAAGGCCGGTGTCATAGTGCCCTTAGGAGCTTCCCGCCCGGGCGCATCCCCCCTTTTGCACTATGACAGCGACCCCCCTCCCCAACCTGTTCTTACGGGCCCCGGACATAACCCACGTGGCCCCCCCTTACTGCCTCAACGCCACCTGGCAGGCCGAAACGGCCATGCACACCAGCAAAACGGACTCCGCTTGCGTGGCCGTGCGGAGTTACCTGGTCCGCGCCTCCTGTGAGACCAGCGGCACAATCCACTGCTTTTTCTTTGCGGTATACAAGGACCCCCACCATCCCCCTCCGCTGATTACCGAGCTCCGCAACTTTGCGGACCTGGTTAACCACCCGCCGGTCCTACGCGAACTGGAGGATAAGCGCGGGGTGCGGCTGCGGTGTGCGCGGCTGCGGTGTGCGCGGCCGTTTAGCGTCGGGACGATTAAGGACGTCTCTGGGTCCGGCGCGTCCTCGGCGGGAGAGTACACGATAAACGGGATCGTGTACCACTGCCACTGTCGGTATCCGTTCTCAAAAACATGCTGGATGGGGGCCTCCGCGGCCCTACAGCACCTGCGCTCCATCAGCTCCAGCGGCATGGCCGCCCGCGCGGCAGAGCATCGACGCGTCAAGATTAAAATTAAGGCGTGATCTCCAACCCCCCATGAATGTGTGTAACCCCCCCCCCCCAAAAAAATAAAGAGCCGTAACCCAACCAAACCAGGCGTGGTGTGAGTTTGTGGACCCAAAGCCCTCAGAGACAATGCGACAGGCCAGTATGGACCGTGATACTTTTATTTATTAACTCACAGGGGCGCTTACCGCCACAGGAATACCAGAATAATGACCACCACAATCGCGACCAGCCCTGTCGCCGGATGGGGCATGATCAGACGAGCCGCGCGCCGCGCGTTGGGCCCTGTACAGCTCGCGCGAATTGACCCTAGGAGGCCGCCACGCGCCCGAGTTTTGCGTTCGTCGCTGGTCGTCGGGCGCCAAAGCCCCGGACGGCTGTTCGGTCGAACGAACGGCCACGACAGTGGCATAGGTTGGGGGGTGGTCCGACATAGCCTCGGCGTACGTCGGGAGGCCCGACAAGAGGTCCCTTGTGATGTCGGGTGGGGCCACAAGCCTGGTTTCCGGAAGAAACAGGGGGGTTGCCAATAACCCGCCAGGGCCAAAACTCCGGCGCTGCGCACGTCGTTCGGCGCGGCGCCGGGCGCGCCGAGCGGCTCGCTGGGCGGCTTGGCGTGAGCGGCCCCGCTCCGACGCCTCGCCCTCTCCGGAGGAGGTTGGCGGAATTGGCACGGACGACAGGGGCCCAGCAGAGTACGGTGGAGGTGGGTCCGTGGGGGTGTCCAGATCAATAACGACAAACGGCCCCTCGTTCCTACCAGACAAGCTATCGTAGGGGGGCGGGGGATCAGCAAACGCGTTCCCCGCGCTCCATAGACCCGCGTCGGGTTGCGCCGCCTCCGAAGCCATGGATGCGCCCCAAAGCCACGACTCCCGCGCGCTAGGTCCTTGGGGTAAGGGAAAAGGCCCTACTCCCCATCCAAGCCAGCCAAGTTAACGGGCTACGCCTTCGGGGATGGGACTGGCACCCCGGCGGATTTTGTTGGGCTGGTACGCGTCGCCCAACCGGGCACGGACGACAGGGGCCCAGCAGAGTACGGTGGAGGTGGGTCCGTGGGGGGGGCCAGGTCAATAACGACAAACGGCCCCTCGTTCCTACCGACAAGCTATCGTAGGGGGGCGGGGGATCAGCAAACGCGTTCCCCGCGCTCCATAGACCCGCGTCGGGTTGCGCCGCCTCCGAAGCCATGGATGCGCCCCAAAGCCACGACTCCCGCGCGCTAGGTCCTTGGGGTAAGGGAAAAGGCCCTACTCCCCATCCAAGCCAGCCAAGTTAACGGGCTACGCCTTCGGGGATGGGACTGGCACCCCGGCGGATTTTGTTGGGCTGGTACGCGTCGCCCAACCGAGGGCCGCGTCCACGGGACGCGCCTTTTATAACCCCGGGGTCATTCCCAACGATCACATGCAATCTAACTGGCTCCCCTCTCCCCTCTCCCCCCCTCTCCCCGCTGGGGCTGGGGAGGGCTGGGGCTGGGGAGGGGCGGTGGTGTGTAGCAGGAGCGGTGTGTTGCGCCGGGGTACGTCTGGAGGAGCGGGAGGTGCGCGGTGACGTGTGGATGAGGAACAGGAGTTGTTGCGCGGTGAGTTGTCGCTGTGAGTTGTGTTGTTGGGCAGGTGTGGTGGATGACGTGACGTGTGACGTGCGGATTGCGCCGTGCTTTGTTGGTGTTGTTTTACCTGTGGCAGCCCGGGCCCCCCGCGGGCGCGCGCGCGCGCAAAAAAGGCGGGCGGCGGTCCGGGCGGCGTGCGCGCGCGCGGCGGGCGTTGGGGGCGGGGCCGCGGGAGCGGGGGAGGAGCGGGGGAGGAGCGGGGGAGGAGCGGGGGAGGAGCGGGGGGGGGAGCGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGAGGGGGGGGGGGAGGAGCGGGGGAGGAGCGGGGCCGCGCGCGGCCCCCGGGGGGTGTGTTTTGGGGGGGCCCGTTTCCGGGGTCTGGCCGCTCCTCCCCCGCTCCTCCCCCCGCTCCTCCCCCCGCTCCTCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCACCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCGCCCCCCCCCCGCTCCCCCCCCGCTCCTCCCCCGCTCCCGCGGCCCCGCCCCCAACGCCCGCCGCGCGCGCGCACGCCGCCCGGACCGCCGCCCGCCTTTTTTGCGCGCGCGCGCGCCCGCGGGGGGCCCGGGCTGCCACAGGTAAAACAACACCAACAAAGCACGGCGCAATCCGCACGTCACACGTCACGTCATCCACCACACCTGCCCAACAACACAACTCACAGCGACAACTCACCGCGCAACAACTCCTGTTCCTCATCCACACGTCCCCGCGCCCCTCCCGCTCCTCCAGACGTACCCCGGCGCAACACACCGCTCCTGCTACACACCACCGCCCCTCCCCAGCCCCAGCCCTCCCCACCCCACCCCCCCCCCCCCCCCCCCCCCCCCGCCCCCACCCCCCCCCCCCCCCCCACCCCCCCCCCCCCCCCCCCCCACCCCAGCCCCCCCCAGCCCCAGCCCTCCCCAGCCCCAGCCCTCCCCAGCCGCGTCCCGCGCTCCCTCGGGGGGGTTCGGGCATCTCTACCTCAGTGCCGCCAATCTCAGGTCAGAGATCCAAACCCTCCGGGGGCGCCCGCGCACCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCACCCCCCGGGGGGGGGGGGGGGAGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGTGGGGGTGCGCGGGCGCCCCCGGAGGGTTTGGATCTCTGACCTGAGATTGGCGGCACTGAGGTAGAGATGCCCGAACCCCCCCGAGGGAGCGCGGGACGCGGCTGGGGAGGGCTGGGGCTGGGGAGGGCTGGGGCTGGGGAGGGCTGGGGCTGGGGGGGGGGGGGGGGGGGGAGGGCGGGGGGGGGGGGGGGCCCCCCCCCCGCCCCCCTCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCGCCCCTCCCCCCCTCCCGCCCCTCGAATAAACAACGCTACTGCAAAACTTAATCAGGTCGTTGCCGTTTATTGCGTCTTCGGGTTTCACAAGCGCCCCGCCCCGTCCCGGCCCGTTACAGCACCCCGTCCCCCTCGAACGCGCCGCCGTCGTCTTCGTCCCAGGCGCCTTCCCAGTCCACAACGTCCCGTCGCGGGGGCGTGGCCAAGCCCGCCTCCGCCCCCAGCACCTCCACGGCCCCCGCCGCCGCCAGCACGGTGCCGCTGCGGCCCGTGGCCGAGGCCCAGCGAATCCCGGGCGGCGCCGGCGGCAGGGCCCCCGGGCGGTCGTCGGCGCGCCGCGCAGCACCAGCGGGGGGGCGTCGTCGTCGGGCTCCAGCAGGGCGCGGGCGCAAAAGTCCCTCCGCGGCCCGCGCCACCGGGCCGGGCCGGCGCGCACCGCCTCGCGCCCCAGCGCCACGTACACGGGCCGCAGCGGCGCGCCCAGGCCCCAGCGCGCGCAGGCGCGGTGCGAGTGGGCCTCCTCCTCGCAGAAGTCCGGCGCGCCGGGCGCCATGGCGTCGGTGGTCCCCGAGGCCGCCGCCCGGCCGTCCAGCGCCGGCAGCACGGCCCGGCGGTACTCGCGCGGGGACATGGGCACCGGCGTGTCCGGGCCGAAGCGCGTGCGCACGCGGTAGCGCACGTTGCCGCCGCGGCACAGGCGCAGCGGCGGCGCGTCGGGGTACAGGCGCGCGTGCGCGGCCTCCACGCGCGCGAAGACCCCCGGGCCGAACACGCGGCCCGAGGCCAGCACCGTGCGGCGCAGGTCCCGCGCCGCCGGCCAGCGCACGGCGCACTGCACGGCGGGCAGCAGGTCGCACGCCAGGTAGGCGTGCTGCCGCGACACCGCGGGCCCGTCGGCGGGCCAGTCGCAGGCGCGCACGGTGTTGACCACGATGAGCCGCCGGTCGCCGGCGCTGGCGAGCAGCCCCAGAAACTCCACGGCCCCGGCGAAGGCCAGGTCCCGCGTGGACAGCAGCAGCACGCCCTGCGCGCCCAGCGCCGACACGTCGGGGGCGCCGGTCCAGTTGCCCGCCCAGGCGGCCGTGTCCGGCCCGCACAGCCGGTTGGCCAGGGCCGCCAGCAGGCAGGACAGCCCGCCGCGCTCGGCGGACCACTCCGGCGGCCCCCCCGAGGCCCCGCCGCCGGCCAGGTCCTCGCCCGGCAGCGGCGAGTACAGCACCACCACGCGCACGTCCTCGGGGTCGGGGATCTGGCGCATCCAGGCCGCCATGCGGCGCAGCGGGCCCGAGGCGCGCAGGGGGCCAAAGAGGCGGCCCCCGGCGGCCCCGTGGGGGTGGGGGTTCTCGTCGTCGTCGCCGCCGCACGCGGCCTGGGCGGCGGGGGCGGGCCCGGCGCACCGCGCGGCGATCGAGGCCAGGGCCCGCGGGTCAAACATGAGGGCCGGTCGCCAGGGGACGGGGAACAGCGGGTGGTCCGTGAGCTCGGCCACGGCGCGCGGGGAGCAGTAGGCCTCCAGGGCGGCGGCCGCGGGCGCCGCCGTGGGCTGGGCCCCCGGGGCTGCCGCCGCCAGCCGCCCAGGGGGTCGGGGCCCTCGGCGGGCGGGCGCGACAGCGCCACGGGGCGCGGGCGGGCCTGCGCCGCGGCGCCCCGGGCCGCCGCGGGCTGGGCGGGTGTGTGCTCGGGCCCAGGCCGCGTGCGGCGGCGACGACGACGAGAACCCCCACCCCCACGGGGCCGCCGGGGCCGCCTCTTTGGCCCCCTGCGCGCCTCGGGCCCGCTGCGCCGCATGGCGGCCTGGATGCGCCAGATCCCCGACCCCGAGGACGTGCGCGTGGTGGTGCTGTCTCGCCGCTGCCGGGCGAGGACCTGGCCGGCGGCGGGGCCTCGGGGGGGCCGCCGGGGGTCCGCCGAGCGCGGCGGGCTGTCCTGCCTGCTGGCGGCCCTGGCCAACCGGCTGTGCGGGCCGGACACGGCCGCCTGGGCGGGCAACTGGACCGGCGCCCCCGACGTGTCGGCGCTGGGCGCGCAGGGCGTGCTGCTGCTGTCCACGCGGGACCTGGCCTTCGCCGGGGCCGTGGAGTTTCTGGGGCTGCTCGCCAGCGCCGGCGACCGGCGGCTCATCGTGGTCAACACCGTGCGCGCCTGCGACTGGCCCGCCGACGGGCCCGCGGTGTCGCGGCAGCACGCCTACCTGGCGTGCGACCTGCTGCCCGCCGTGCAGTGCGCCGTGCGCTGGCCGGCGGCGCGGGACCTGCGCCGCACGGTGCTGGCCTCGGGCCGCGTGTTCGGCCCGGGGGTCTTCGCGCGCGTGGAGGCCGCGCACGCGCGCCTGTACCCCGACGCGCCGCCGCTGCGCCTGTGCCGCGGCGGCAACGTGCGCTACCGCGTGCGCACGCGCTTCGGCCCGGACACGCCGGTGCCCATGTCCCCGCGCGAGTACCGCCGGGCCGTGCTGCCGGCGCTGGACGGCCGGGCGGCGGCCTCGGGGACCACCGACGCCATGGCGCCCGGCGCGCCGGACTTCTGCGAGGAGGAGGCCCACTCGCACCGCGCCTGCGCGCGCTGGGGCCTGGGCGCGCCGCTGCGGCCCGTGTACGTGGCGCTGGGGCGCGAGGCGGTGCGCGCCGGCCCGGCCCGGTGGCGCGGGCCGCGGAGGGACTTTTGCGCCCGCGCCCTGCTGGAGCCCGACGACGACGCCCCCCCGCTGGTGCTGCGCGGCGACGACGACGACGGCCCGGGGGCCCGCCGCCGGCGCCGCCCGGGATTCGCTGGGCCTCGGCCACGGGCCGCAGCGGCACCGTGCTGGCGGCGGCGGGGGCCGTGGGGTGCTGGGGGCGGAGGCGGGCTTGGCCACGCCCCCGCGACGGGACGTTGTGGACTGGGAAGGCGCCTGGGACGAAGACGACGGCGGCGCGTTCGAGGGGGACGGGGTGCTGTAACGGGCCGGGACGGGGCGGGGCGCTTGTGAAACCCGAAGACGCAATAAACGGCAACGACCTGATTAAGGTTTGCAGGAGCGTTGTTTATTCGAGGGGCGGGAGGGGGCGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGCGGCGGCGCCCGCGGCCGCCGCCCTGGAGGCCTACTGCTCCCCGCGCGCCGTGGCCGAGCTCACGGACCCCCCGCTGTTCCCCGTCCCCTGGCGACCGGCCCTCATGTTTGCCCCGCGGGCCCTGGCCTCGATCGCCGCGCGGTGCGCCGGGCCCGCCCCCGCCGCCCTGGGTGGGTGGGGAGTGGGTGGGTGGGGAGTGGGTGGGTGGGGAGTGGCAAGGAAGAAACAAGCCCGACCACCAGACAGAAAATGTAACCATACCCAAACCGACTCTGGGGGCTGTTTGTGGGGTCGGAACCATAGGATGAACAAACCACCCCGTACCTCCCGCACCCAAGGGTGCGGGTGGCTCATCGGCATCTGTCCGGTATGGGTTGTTCCCCACCCACTCGCGTTCGGACGTCTTAGAATCATGGCGGTTTTCTATGCCGACATCGGTTTTCTCCCCCGCAATAAGACACGATGCGATAAAATCTGTTTGTAAAATTTATTAAGGGTACAAAATGCCCTAGCACAGGGGTGGGGGTAGGGCCGGGGCCCCACACCCAAACGCACCAAACAGATGCAGGCAGTGGGTCGAGTACAGCCCCGCGTACGAACACGTCGATGCGTGTGTCAGACAGCACCAGAAAGCACAGGCCATCAACAGGTCGTGCATGTGTCGGTGGGTTTGGACGCGGGGGGCCATGGTGGTGATAAAGTTAATGGCCGCCGTCCGCCAGGGCCACAGGGGCGCCGTCTCTTGGTTGGCCCGGAGCCACTGGGTGTGGACCAGCCGCGCGTGGCGGCCCAACATGGCCCCTGTAGCCGGGGGCGGGGGATCGCGCACGTTTGCAGCGCACATGCGAGACACCTCGACCACGGTTCGAAAGAAGGCCCGGTGGTCCGCGGGCAACATCACCAGGTGCGCAAGCGCCCGGGCGTCCAGAGGGTAGAGCCCTGAGTCATCCGAGGTTGGCTCATCGCCCGGGTCTTGCCGCAAGTGCGTGTGGGTTGGGCTTCCGGTGGGCGGGACGCGAACCGCGGTGTGGATCCCGACGCGGGCCCGAGCGTATGCTCCATCTTGTGGGGAGAAGGGGTCTGGGCTCGCCAGGGGGGCATACTTGCCCGGGCTATACAGACCCGCGAGCCGTACGTGGTTCGCGGGGGGTGCGTGGGGTCCGGGGTCCCTGGGAGACCGGGGTTGTCGTGGATCCCTGGGGTCACGCGGTACCCTGGGGTCTCTGGGAGCTCGCGGTACTCTGGGTCCCTAGGTTCTCGGGGTGGTCGCGGACCCGGGGCTCCCGGGGAACACGCGGTGTCCTGGGGATTGTTGGCGGTCGGACGGCTTCAGATGGCTTCGAGATCGTAGTGTCCGCACCGACTCGTAGTAGACCCGAATCTCCACATTGCCCCGCCGCTTGATCATTATCACCCCGTTGCGGGGGTCCGGAGATCATGCGCGGGTGTCCTCGAGGTGCGTGAACACCTCTGGGGTGCATGCCGGCGGACGGCACGCCTTTTAAGTAAACATCTGGGTCGCCCGGCCCAACTGGGGCCGGGGGTTGGGTCTGGCTCATCTCGAGAGACACGGGGGGGAACCACCCTCCGCCCAGAGACTCGGGTGATGGTCGTACCCGGGACTCAACGGGTTACCGGATTACGGGGACTGTCGGTCACGGTCCCGCCGGTTCTTCGATGTGCCACACCCAAGGATGCGTTGGGGGCGATTTCGGGCAGCAGCCCGGGAGAGCGCAGCAGGGGACGCTCCGGGTCGTGCACGGCGGTTCTGGCCGCCTCCCGGTCCTCACGCCCCCTTTTATTGATCTCATCGCGTACGTCGGCGTACGTCCTGGGCCCAACCCGCATGTTGTCCAGGAAGGTGTCCGCCATTTCCAGGGCCCACGACATGCTTTTCCCGACGAGCAGGAAGCGGTCCACGCAACGGTCGCCGCCGGTCGCCTCGACGAGGGCGTTCCTCCTGCGGGAAGGCACGAACGCGGGTGAGCCCCCTCCTCCGCCCCCGCGTCCCCCCTCCCCCGCCCCCGCGTCCCCCCCCTCCGCCCCCGCGTCCCCCCCTCCTCCGCCCCCGCGTCCCCCCCCCTCCGCCCCCGCGTCCCCCCTCCTCCCCCCCCAAGGTGCTTACCCGTGCAAAAAGGCGGACCGGTGGGTTTCTGTCGTCGGAGGCCCCCGGGGTGCGTCCCCTGTGTTTCGTGGGTGGGGTGGGCGGGTCTTTCCCCCCCGCGTCCGCGTGTCCCTTTCCGATGCGATCCCGATCCCGAGCCGGGGCGTCGCGATGCCGACGCCGTCCGCTCCGACGGCCCTCTGCGACTCCCGCTCCCGGTCCGCGTGCTCCGCAGCCGCTCCCGTCGTTCGTGGCCGGCGCCGTCTGCGGGCGTCGGTCGCGCCGGGCCTTTATGTGCGCCGGAGAGACCCGCCCCCCGCCGCCCGGGTCCGCCCCCGGGGCCGGCGCGGAGTCGGGCACGGCGCCAGTGCTCGCACTTCGCCCTAATAATATATATATATTGGGACGAAGTGCGAACGCTTCGCGTTCTCACTTCTTTTCCCCGGCGGCCCCGCCCCCTTGGGGCGGTCCCGCCCGCCGGCCAATGGGGGGGCGGCAAGGCGGGCGGCCCTTGGGCCGCCCGCCGTCCCGTTGGTCCCGGCGTCCGGCGGGCGGGACCGGGGGCCCGGGGACGGCCAACGGGCGCGCGGGGCTCGATCTCATTACCGCCGAACCGGGAAGTCGGGGCCCGGGCCCCGCCCCCTGCCCGTTCCTCGTTAGCATGCGGAACGGAAGCGGAAACCGCCGGATCGGGCGGTAATGAGATGCCATGCGGGGCGGGGCGCGGACCCACCCGCCCTCGCGCCCCGTCCATGGCAGATGGCGCGGATGGGCGGGGCCGGGGGTTCGACCAACGGGCCGCGGCCACGGGCCCCCGGCGTGCCGGCGTCGGGGCGGGGTCGTGCATAATGGAATTCCGTTCGGGGTGGGCCCGCCGGGGGGCGGGGGGGCGGCGGCCTCCGCTGCTCCTCCTTCCCGCCGGCCCCTGGGACTATATGAGCCCGAGGACGCCCCGATCGTCCACACGGAGCGCGGCTGCCGACACGGATCCACGACCCGACGCGGGACCGCCAGAGACAGACCGTCAGACGCTCGCCGCGCCGGGACGCCGATACGCGGACGAAGCGCGGGAGGGGGATCGGCCGTCCCTGTCCTTTTTCCCCACCCAAGCATCGACCGGTCCGCGCTAGTTCCGCGTCGACGGCGGGGGTCGTCGGGGTCCGTGGGTCTCGCCCCCTCCCCCCTCGAGAGTCCGTAGGTGACCTACCGTGCTACGTCCGCCGTCGCAGCCGTATCCCCGGAGGATCGCCCCGCATCGGCGATGGCGTCGGAGAACAAGCAGCGCCCCGGCTCCCCGGGCCCCACCGACGGGCCGCCGCCCACCCCGAGCCCAGACCGCGACGAGCGGGGGGCCCTCGGGTGGGGCGCGGAGACGGAGGAGGGCGGGGACGACCCCGACCACGCCCCGACCACCCCCACGACCTCGACGACGCCCGGCGGGACGGGAGGGCCCCCGCGGCGGGCACCGACGCCGGCGAGGACGCCGGGGACGCCGCTCGCCGCGACAGCTGGCTCTGCGGCCTCCCTGGTAGAGGAGGCCGGCCGGACGATCCCGACGCCCGACCCCGCGGCCTCGCCGCCCCGGACCCCCGCCTTTCTAGCCGACGACGATGACGGGGACGAGTACGACGACGCAGCCGACGCCGCCGGCGACCGGGCCCCGGCCCGGGGCCGCGAACGGGAGGCCCCGCTACGCGGCGCGTATCCGGACCCCACGGACCGCCTGTCCCGCGCCCGCCGGCCCAGCCGCCGCGGAGACGTCGTCACGGCCGGCGGCGGCCATCGGCGCATCGACCTCGGCGGACTCCGGGTCCTCGTCCTCGTCGTCCGCATCCTCTTCGTCCTCGTCGTCCGACGAGGACGAGGACGACGACGGCAACGACGCGGCCGACCACGCACGCGAGGCGCGGGCCGTCGGGCGGGGTCCGTCGAGCGCGGCGCCGGAAGCCCCCGGGCGGACGCCGCCCCCGCCCGGGCCACCCCCCCTCTCCGAGGCCGCGCCCAAGCCCCGGGCGGCGGCGAGGACCCCCGCGGCCTCCGCGGGCCGCATCGAGCGCCGCCGGGCCCGCGCGGCGGTGGCCGGCCGCGACGCCACGGGCCGCTTCACGGCCGGGCAGCCCCGGCGGGTCGGGCTGGACGCCGACGCGGCCTCCGGCGCCTTCTACGCGCGCTATCGCGACGGGTACGTCAGCGGGGAGCCGTGGCCCGGCGCCGGGCCCCCGCCCCCGGGGCGGGTGCTGTACGGCGGCCTGGGCGACAGCCGCCCGGGCCTCTGGGGGGCGCCCGAGGCGGAGGAGGCGCGACGCCGGTTCGAGGCCTCGGGCGCCCCGGGGCCGTGTGGGGCCCGAGCGGGGAGACGCCGCGCAGCAGACGCCCTGATCACGCGGCTGCTGTACACCCCGGACGCGGAGGCCAGTCTGGGGCTCCAGACCCGCGTGGTCCCCGGGGACGTGGCGCTGGACCAGGCCTGCTTCCGGATCTCGGGCGCCGCGCGCAACAGCAGCTCCTTCATCCCGGCAGCGTGGCGCGGGCCGTGCCCCACCTGGGCTACGCCATGGCGGCCGGCCGCTTCGGCTGGGGCCTGGCGCACGCGGCGGCCGCCGTGGCCATGAGCCGCCGATACGACCGCGCGCAGAAGGGCTTCCTGCTGACCAGCCTGCGCCGCGCCTACGCGCCCCTGTTGGCGCGCGAGAACGCGGCGCTGACGGGGGCCGCGGGGAGCCCCGGCGCCGGCGCAGATGACGAGGGGGTCGCCGCCGTCGCCGCCGCCGCACCGGGCGGCGCGCGGGCCCGCCGGGTACGGCGCCGCGGGGATCCTCGCCGCCCTGGGGCGGCTGTCCGCCGCGCCCGCCTCCCCCGTGGGGGGCGACGACCCCGACGCCGCCCGCCACGCCGACGCCGACCCGGGCGCCGCGCCCAGGCCGGCCGCGTGGCCGTCGAGTGCCTGGCCGCCTGCCGCGGGTCCTGGCGGCGCTGGCCGAGGGCTTCGACGGCGACCTGGCGGCCGTCCCGGGGCTGGCCGGGGCCCGGCCCGCCAGCCCCCCGCGCCGGAGGGACCCGCGGACCCCGCTTCCCCGCCGCCGCCGCACGCCGACGCGCCCCGCCTGCGCGCGGGCTGCGCGGCGCGGTCGTGCGCGCCGCGCTGGTGCTCATGCCCCTGCGCGGGGACCTGCGCGTGGCCGGCGGCAGCGGGCCGCCGTGGCCGCCGTGCGCGCCGGAGCCTGGTCGCCGGGGCCCTGGGCCCCGCGCTGCCGCGGGACCCGCGCCTGCCGAGCTCCGCGGCCGCCGCCGCCGCGGACCGCTGTTTGAGAACCAGAGCCTCCGCCCCCTGCTGGCGGCGGCGGCCAGCGCACCGGACGCCGCCGACGCGCTGGCGGCCGCCGCCGCCTCCGCCGCCCGCGGGAGGGGCGCAAGCGCAAGAGTCCCGGCCCGGCCCGGCCGCCCGGAGGCGGCGGCCCGCGACCCCCGAAGACGAAGAAGAGCGGCGCGGACGCCCCCCCCGCGCGCCCCCCGCCCCCCCCCCCCCGCCCCCCCCCCCCCCCCCCCGGGGCCCGAGCCCCCCCCCGCCCAGCCCGCGGCGGCCCGGGGCGCCGCGGCGCAGGCCCGCCCGCGCCCCGTGGCGCTGTCGCGCCGGCCCGCCGAGGGCCCCGACCCCCTGGGCGGCTGGCGGCGGCAGCCCCGGGGGCCCAACCCCACAGCGGCGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGCGGGCGGCCGGGCCGGGGGCGTCCGCGCCGCTCTTCTTCGTCTTCGGGGGTCGCGGGCCGCCGCCTCCGGGCGGCCGGGCCGGGCCGGGACTCTTGCGCTTGCGCCCCTCCCGCGGCGCGGCGGGGGCGGCGGCGGCCGCCAGCGCGTCGGCGGCGTCCGGTGCGCTGGCCGCCGCCGCCAGCAGGGGGCGGAGGCTCTGGTCTCAAACAGCAGGTCCGCGGCGGCGGCGGCCGCGGAGCTCGGCAGGCCGGTCCCGCGGCAGCGCGGGACAAGGGCCCCGGCGACCAGGCTCACGGCGCGCACGGCGGCCACGGCGGCCTCGCTGCCGCCGGCCACGCGCAGGTCCCCGCGCAGGCGCATGAGCACCAGCGCGTCGCGCACGAACCGCAGCTCGCGCAGCCACGCGCGCAGGCGGGGCGCGTCGGCGTGCGGCGGCGGCGGGGAAGCGGGGTCCGCGGGTCCCTCCGGCCGCGGGGGGCTGGCGGGCCGGGCCCCGGCCAGCCCCGGGACGGCCGCCAGGTCGCCGTCGAAGCCCTCGGCCAGCGCCTCCAGGATCCCGCGGCAGGCGGCCAGGCACTCGACGGCCACGCGGCCGGCCTGGGCGCGGCGCCCGGCGTCGGCGTCGGCGTGGCGGGCGGCGTCGGGGTCGTCGCCCCCCACGGGGGAGGCGGGCGCGGCGGACAGCCGCCCCAGGGCGGCGAGGATCCCCGCGGCGCCGTACCCGGCGGGCACCGCGCGCTCGCCCGGTGCGGCGGCGGCGACGGCGGCGACCCCCTCGTCATCTGCGCCGGCGCCGGGGCTCCCCGCGGCCCCCGTCAGCGGGTGGGAACAGGGGCGCGTAGGCGCGGCGCAGGCTGGTCAGCAGGAAGCCCTTCTGCGCCTCGTATCGGCGCTCATGGCCACGGCGGCCGCCGCGTGCGCCAGGCCCCAGCCGAAGCGGCCGGCCGCCATGGCGTAGCCCAGGTGGGGCACGGCCCGCGCCACGCTGCCGGTGATGAAGGAGCTGCTGTTGCGCGCGGCGCCCGAGATCCGGAAGCAGGCCTGGTCCAGCGCCACGTCCCCGGGGACCACGCGCGGGTTCTGGAGCCACCCCTGGCCTCCGCGTCCGGGGTGTACAGCAGCCGCGTGATCAGGGCGTACTGCTGCGCGGCGTCGCCCAGCTCGGGCGCCCACACGGCCGCCGGGGCGCCCGAGGCCTCGAACCGGCGTCGCGCCTCCTCCGCCTCGGGCGCCCCCCAGAGGCCCGGGCGGCTGTCGCCCAGGCCGCCGTACAGCACCCGCCCCGGGGGCGGGGGCCCGGCGCCGGGCCACGGCTCCCCGCTGACGTACCCGTCGCGATAGCGCGCGTAGAAGGCGCCGGAGGCCGCGTCGGCGTCCAGCTCGACCCGCCGGGGCTGCCCGGCCGTGAAGCGGCCCGTGGCGTCGCGGCCGGCCACCGCCGCGCGGGCCCGGCGGCGCTCGATGCGGCCCGCGGAGGCCGCGGGGGTCCGCGCCGCCGCCCGGGGCTTGGGCGCGGCCTCGGAGAGGGGGGGTGGCCCGGGCGGGGGCGGCGTCCGCCCGGGGGCTTCCGGCGCCGCGCTCGACGGACCCCGCCCGACGGCCCGCGCCCGCGGCGTGGTCGGCCGCGTCGTTGCCGTCGTCGTCCCGTCCTCGTCGGACGACGGGACGAAGCGGATGCGGACGGCGAGGACGAGGACCCGGAGTCCGGCGAGGCCGAGACGCCGATGGCCGCCGCCGGCCGTGACGACGTCTCCGCGGCGGCTGGGCCGGCGGGCGCGGCGACAGGCGGTCCGTGGGGTCCGGATACGCGCCGCGTAGCGGGGCCTCCCGTTCGCGGCCCCGGGCCGGGGCCCGGTCGCCGGCGGCGTCGGCTGCGTCGTCGTACTCGTCCCCGTCATCGTCGTCGGCTAGAAAGGCGGGGGCCGGGGCGGCGAGGCCGCGGGGTCGGGCGTCGGGATCGTCCGGACGGCCTCCTCTACCATGGAGGCCAGCGAGCCAGCTGTCGCGGCGAGACGGCGTCCCCGGCGTCCTCGCCGGCGTCGGTGCCCGCCGCGGGGGCCCTCCCGTCCCGCCGGGCGTCGTCGAGGTCGTGGGGGTGGTCGGGGTCGTGGTCGGGGTCGTCCCCGCCCTCCTCCGTCTCCGCGCCCCACCCGAGGGCCCCCCGCTCGTCGCGGTCTGGGCTCGGGGGGGCGGCGGCCCGTCGGTGGGGCCCGGGGGCCGGGGCGCTGCTTGTTCTCCGACGCCATCGCCGATGCGGGGCGATCCTCCGGGGATACGGCTGCGACGGCGGACGTAGCACGGTAGGTCACCTACGGACTCTCGATGGGGGGAGGGGGCGAGACCCACGGACCCCGACGACCCCCGCCGTCGACGCGGAACTAGCGCGGACCGGTCGATGCTTGGGTGGGGAAAAAGGACAGGGACGGCCGATCCCCCTCCCGCGCTTCGTCCGCGTATCGGCGTCCCGGCGCGGCGAGCGTCTGACGGTCTGTCTCTGGCGGTCCCGCGTCGGGTCGTGGATCCGTGTCGGCAGCCGCGCTCCGTGTGGACGATCGGGGCGTCCTCGGGCTCATATAGCCCAGGGGCCGGCGGGAAGGAGGAGCAGCGGAGGCCGCCGGCCCCCCGCCCCCCGGCGGGCCCACCCCGAACGGAATTCCATTATGCACGACCCCGCCCCGACGCCGGCACGCCGGGGGCCCGTGGCCGCGGCCCGTTGGTCGAACCCCCGGCCCCGCCCATCCGCGCCATCTGCCATGGACGGGGCGCGAGGGCGGGTGGGTCCGCGCCCCGCCCCGCATGGCATCTCATTACCGCCCGATCCGGCGGTTTCCGCTTCCGTTCCGCATGCTAACGAGGAACGGGCAGGGGGCGGGGCCCGGGCCCCGACTTCCCGGTTCGGCGGTAATGAGATACGAGCCCCGCGCGCCCGTTGGCCGTCCCCGGGCCCCCGGTCCCGCCCGCCGGACGCCGGGACCAACGGGACGGCGGGCGGCCCAAGGGCCGCCCGCCTTGCCGCCCCCCCATTGGCCGGCGGGCGGGACCGCCCCAAGGGGGCGGGGCCGCCGGGTAAAAGAAGTGAGAACGCGAAGCGTTCGCACTTCGTCCCAATATATATATATTATTAGGGCGAAGTGCGAGCACTGGCGCCGTGCCCGACTCCGCGCCGGCCCCGGGGGAGGGAGGAGGGGGGCGGGTCTCTCCGGCGCACATAAAGGCCCGGCGCGACCGACGCCCGCAGACGGCGCCGGCCACGAACGACGGGAGCGGCTGCGGAGCACGCGGACCGGGAGCGGGAGTCGCAGAGGGCCGTCGGAGCGGACGGCGTCGGCATCGCGACGCCCCGGCTCGGGATCGGGATCGCATCGGAAAGGGACACGCGGACGCGGGGGGGAAAGACCCGCCCACCCCACCCACGAAACACAGGGGACGCACCCCGGGGGCCTCCGACGACAGAAACCCACCGGTCCGCCTTTTTTGCACGGGTAAGCACCTTGGGGGGGGGAGGAGGGGGGACGCGGGGGCGGAGGAGGGGGGACGCGGGGGCGGAGGAGGGGGGACGCGGGGGCGGGGGGGGGGGCGCGGGGGCGGAGGAGGGGGGGACGCGGGGGGGGGGGGGGGGGGCGCGGGGGCGGAGGAGGGGGCTCACCCGCGTTCGTGCCTTCCCGCAGGAGGAACGCCCTCGTCGAGGCGACCGGCGGCGACCGTTGCGTGGACCGCTTCCTGCTCGTCGGGGGGGGGGGGAGCCACTGTGGTCCTCCGGGACGTTTTCTGGATGGCCGACATTTCCCCAGGCGCTTTTGTGCCTTGTGTAAAAGCGCGGCGTCCCGCTCTCCGATCCCCGCCCCTGGGCACGCGCAAGCGCAAGCGCCCTGCCCGCCCCCTCTCATCGGAGTCTGAGGTCGAATCCGAGACAGCCTTGGAGTCTGAGGTCGATCCGAGACAGCATCGGATTCGACCGAGTCTGGGGACCAGGAGGAAGCCCCGCATCGGTGGCCGTAGGGCCCCCCGGAGGCTTGGGGGGCGGTTTTTTCTGGACATGTCGGCGGAATCCACCACGGGGACGGAAACGGATGCGTCGGTGTCGGACGACCCCGACGACACGTCCGACTGGTCTTGTGACGACATTCCCCCACGACCCAAGCGGGCCCGGGTAAACCTGCGGCTCACTAGCTCTCCCGATCGGCGGGATGGGGTTATTTTTCCTAAGATGGGGCGGGTCCGGTCTACCCGGGAAACGCAGCCCCGGGCCCCCACCCCGTCGGCCCCAAGCCCAAATGCAATGCTCCGGCGCTCGGTGCGCCAGGCCCAGAGGCGGAGCAGCGCACGATGGACCCCCGACCTGGGCTACATGCGCCAGTGTATCAATCAGCTGTTTCGGGTCCTGCGGGTCGCCCGGGACCCCCACGGCAGTGCCAACCGCCTGCGCCACCTGATACGCGACTGTTACCTGATGGGATACTGCCGAGCCCGTCTGGCCCCGCGCACGTGGTGCCGCTTGCTGCAGGTGTCCGGCGGAACCTGGGGCATGCACCTGCGCAACACCATACGGGAGGTGGAGGCTCGATTCGACGCCACCGCAGAACCCGTGTGCAAGCTTCCTTGTTTGGAGGCCAGACGGTACGGCCCGGAGTGTGATCTTAGTAATCTCGAGATTCATCTCAGCGCGACAAGCGATGATGAAATCTCCGATGCCACCGATCTGGAGGCCGCCGGTTCGGACCACACGCTCGCGTCCCAGTCCGACACGGAGGATGCCCCCTCCCCCGTTACGCTGGAAACCCCAGAACCCCGCGGGTCCCTCGCTGTGCGTCTGGAGGATGAGTTTGGGGAGTTTGACTGGACCCCCCAGGAGGGCTCCCAGCCCTGGCTGTCTGCGGTCGTGGCCGATACCAGCTCCGTGGAACGCCCGGGCCCATCCGATTCTGGGGCGGGTCGCGCAGCAGAAGACCGCAAGTGTCTGGACGGCTGCCGGAAAATGCGCTTCTCCACCGCCTGCCCCTATCCGTGCAGCGACACGTTTCTCCGGCCGTGAGTCCGGTCGCCCCGACCCCCTTGTATGTCCCCAAAATAAAAGACCAAAATCAAAGCGTTTGTCCCAGCGTCTTAATGGCGGGAAGGGCGGAGAGAAACAGACCACGCGTACATGGGGGGTGTTTGGGGGTTTATTGACATCGGGGCTACAGGGTGGTAACCGGATAGCAGATGTGAGGAAGTCTGGGCCGTTCGCCGCGAACGGCGATCAGAGGGTCCGTTTCTTGCGGACCACGGCCCGGTGATGTGGGTTGCTCGTCTAAAATCTCGGGCATACCCATACACGCACAACACGGACGCCGCACCGAATGGGACGTCGTAAGGGGGTGGGAGGTAGCTGGGTGGGGTTTGTGCAGAGCAATCAGGGACCGCAGCCAGCGCATACAATCGCGCTCCCGTCCGTTGGTCCCGGGCAGGACCACGCCGTACTGGTATTCGTACCGGCTGAGCAGGGTCTCCAGGGGGTGGTTGGGTGCCGCGGGGAACGGGGTCCACGCCACGGTCCACTCGGGCAAAAACCGAGTCGGCACGGCCCACGGTTCTCCCACCCACGCGTCTGGGGTCTTGATGGCGATAAATCTTACCCCGAGCCGGATTTTTTGGGCGTATTCGAGAAACGGCCCACACAGGTCCGCCGCGCCTACCACCCACAAGTGGTAGAGGCGAGGGGGGCTGGGTTGGTCTCGGTGCAACAGTCGGAAGCACGCCACGGCGTCCACGACCTCGGTGCTCTCCAAGGGGCTGTCCTCCGCAAACAGGCCCGTGGTGGTGTTTGGGGGGCAGCGACAGGACCTAGTGCGCACGATCGGGCGGGTGGGTTTGGGTAAGTCCATCAGCGGCTCGGCCAACCGTCGAAGGTTGGCCGGGCGAACGACGACCGGGGTACCCAGGGGTTCTGATGCCAAAATGCGGCACTGCCTAAGCAGGAAGCTCCACAGGGCCGGGCTTGCGTCGACGGAAGTCCGGGGCAGGGCGTTGTTCTGGTCAAGGGGGGGCATTACGTTGACGACAACAACGCCCCTGTTGGGATATTACAGGCCCGTGTCCGGTTTGGGGCACTTGCAGATTTGTAAGGCCACGCACGGCGGGGAGACAGGCCGACGCGGGGGCTGCTCTAAAAATTTAAGGGCCCTACGGTCCACAGACCCGCCTTCCCGGGGGGGCCCTTGGAGCGACCGGCAGCGGAGGCGTCCGGGGGAGGGGAGGGTTATTTACGGGGGGGTAGGTCAGGGGGTGGGTCGTCAAACTGCCGCTCCTTAAAACCCCGGGGCCCGTCGTTCGGGGTGCTCGTTGGTTGGCACTCACGGGGCGGCGAATGGCCTGTCGTAAGTTTTGTCGCGTTTACGGGGGACAGGGCAGGAGGAAGGAGGAGGCCGTCCCGCCGGAGACAAAGCCGTCCCGGGTGTTTCCTCATGGCCCCTTTTATACCCCAGCCGAGGACGCGTGCCTGGACTCCCCGCCCCCGGAGACCCCCAAACCTTCCCACACCACACCACCCGGCGATGCCGAGCGCCGGCATCTGCAGGAGAGGCAGATGGACGGAAACCAGGACTACCCCATAGAGGACGACCCCAGCGCGGATGCCGCGGACGATGTCGACGAGGACGCCCCGGACGACGTGGCCTATCCGGAGGAATACGCAGAGGAGCTTTTTCTGCCCGGGGACGCGACCGGTCCCCTTATCGGGGCCAACGACCACATCCCTCCCCCGCGTGGCGCATCTCCCCCCGGTATACGACGACGCAGCCGGGATGAGATTGGGGCCACGGGATTTACCGCAGAAGAGCTGGACGCCATGGACAGGCAGGCGGCTCGAGCCATCAGCCGCGGCGGCAAGCCCCCCTCGACCAATGGCCAAGCTGGTGACTGGCATGGGCTTTACGATCCACGGAGCGCTCACCCCAGGATCGGAGGGGTGTGTCTTTGACAGCAGCCACCCAGATTACCCCCAACGGGTAATCGTGAAGGCGGGGTGGTACACGAGCACGAGCCACGAGGCGCGACTGCTGAGGCGACTGGACCACCCGGCGATCCTGCCCCTCCTGGACCTGCATGTCGTCTCCGGGGTCACGTGTCTGGTCCTCCCCAAGTACCAGGCCGACCTGTATACCTATCTGAGTAGGCGCCTGAACCCACTGGGACGCCCGCAGATCGCAGCGGTCTCCCGGCAGCTCCTAAGCGCCGTTGACTACATTCACCGCCAGGGCATTATCCACCGCGACATTAAGACCGAAAATTTTTTATTAACACCCCCGAGGACATTTGCCTGGGGGACTTTGGTGCCGCGTGCTTCGTGCAGGGTTCCCGATCAAGCCCCTTCCCCTACGGAATCGCCGGAACCATCGACACCAACGCCCCCGAGGTCCTGGCCGGGGATCCGTATACCACGACCGTCGACATTTGGAGCGCCGGTCTGGTGATCTTCGAGACTGCCGTCCACAACGCGTCCTTGTTCTCGGCCCCCCGCGGCCCCAAAAGGGGCCCGTGCGACAGTCAGATCACCCGCATCATCCGACAGGCCCAGGTCCACGTTGACGAGTTTTCCCCGCATCCAGAATCGCGCCTCCCTCGCGCTACCGCTCCCGCGCGGCCGGGAACAATCGCCCGCCTTACACCCGACCGGCCTGGACCCGCTACTACAAGATGGACATAGACGTCGAATATCTGGTTTGCAAAGCCCTCACCTTCGACGGCGCGCTTCGCCCCAGCGCCGCAGAGCTGCTTTGTTTGCCGCTGTTTCAACAGAAATGACCGCCCCCGGGGGGCGGTGCTGTTTGCGGGTTGGCACAATAAGACCCCGACCCGCGTCTGTGGTGTTTTTGGCATCATGTCGCCGGGCGCCATGCGTGCCGTTGTTCCCATTATCCCATTCCTTTTGGTTCTTGTCGGTGTATCGGGGGTTCCCACCAACGTCTCCTCCACCACCCAACCCCAACTCCAGACCACCGGTCGTCCCTCGCATGAAGCCCCCAACATGACCCAGACCGGCACCACCGACTCTCCCACCGCCATCAGCCTTACCACGCCCGACCACACACCCCCCATGCCAAGTATCGGACTGGAGGAGGAGGAGGAAGAGGAGGAGGGGGCCGGGGATGGCGAACATCTTAAGGGGGGAGATGGGACCCGTGACACCCTACCCCAGTCCCCGGGTCCAGCCGTCCCGTTGGCCGGGGATGACGAGAAGGACAAACCCAACCGTCCCGTAGTCCCACCCCCCGGTCCCAACAACTCCCCCGCGCGCCCCGAGACCAGTCGACCGAAGACACCCCCCACCAGTATCGGGCCGCTGGCAACTCGACCCACGACCCAACTCCCCTCAAAGGGGCGACCCTTGGTTCCGACGCCTCAACATACCCCGCTGTTCTCGTTCCTCACTGCCTCCCCCGCCCTGGACACCCTCTTCGTCGTCAGCACCGTCATCCACACCTTATCGTTTGTGTGTATTGTTGCTATGGCGACACACCTGTGTGGTGGTTGGTCCAGACGCGGGCGACGCACACACCCTAGCGTGCGTTACGTGTGCCTGCCGCCCGAACGCGGGTAGGGTATGGGGCGGGGATGGGGAGAGCCCACACGCGGAAAGCAAGAACAATAAAGGCGGCGGGATCTAGTTGATATGCGTCTCTGGGTGTTTTTGGGGTGTGGTGGGCGCGGGGCGGTCATTGGACGGGGGTGCAGTTAAATACATGCCCGGGACCCATGAAGCATGCGCGACTTCCGGGCCTCGGAACCCACCCGAAACGGCCAACGGACGTCTGAGCCAGGCCTGGCTATCCGGAGAAACAGCACACGACTTGGCGTTCTGTGTGTCGCGATGTCTCTGCGCGCAGTCTGGCATCTGGGGCTTTTGGGAAGCCTCGTGGGGGCTGTTCTTGCCGCCACCCATCTGGGACCTGCGGCCAACACAACGGACCCCTTAACGCACGCCCCAGTGTCCCCTCACCCCAGCCCCCTGGGGGGCTTTGCCGTCCCCCTCGTAGTCGGTGGGCTGTGTGCCGTAGTCCTGGGGGCGGCGTGTCTGCTTGAGCTCCTGCGTCGTACGTGCCGCGGGTGGGGGCGTTACCATCCCTACATGGACCCAGTTGTCGTATAATTTTTTCCCCCCCCCCCTTCTCCGCATGGGTGATGTCGGGTCCAAACTCCCGACACCACCAGCTGGCATGGTATAAATCACCGGTGCGCCCCCCAAACCATGTCCGGCAGGGGGATGGGGGGCGAATGCGGAGGGCACCCAACAACACCGGGCTAACCAGGAAATCCGTGGCCCCGGCCCCCAACAAAGATCGCGGTAGCCCGGCCGTGTGACATTATCGTCCATACCGACCACACCGACGAATCCCCTAAGGGGGAGGGGCCATTTTACGAGGAGGAGGGGTATAACAAAGTCTGTCTTTAAAAAGCAGGGGTTAGGGAGTTGTTCGGTCATAAGCTTCAGTGCGAACGACCAACTACCCCGATCATCAGTTATCCTTAAGGTCTCTTTTGTGTGGTGCGTTCCGGTATGGGGGGGGCTGCCGCCAGGTTGGGGGCCGTGATTTTGTTTGTCGTCATAGTGGGCCTCCATGGGGTCCGCGGCAAATATGCCTTGGCGGATGCCTCTCTCAAGATGGCCGACCCCAATCGCTTTCGCGGCAAAGACCTTCCGGTCCTGGACCAGCTGACCGACCCTCCGGGGGTCCGGCGCGTGTACCACATCCAGGCGGGCCTACCGGACCCGTTCCAGCCCCCCAGCCTCCCGATCACGGTTTACTACGCCGTGTTGGAGCGCGCCTGCCGCAGCGTGCTCCTAAACGCACCGTCGGAGGCCCCCCAGATTGTCCGCGGGGCCTCCGAAGACGTCCGGAAACAACCCTACAACCTGACCATCGCTTGGTTTCGGATGGGAGGCAACTGTGCTATCCCCATCACGGTCATGGAGTACACCGAATGCTCCTACAACAAGTCTCTGGGGGCCTGTCCCATCCGAACGCAGCCCCGCTGGAACTACTATGACAGCTTCAGCGCCGTCAGCGAGGATAACCTGGGGTTCCTGATGCACGCCCCCGCGTTTGAGACCGCCGGCACGTACCTGCGGCTCGTGAAGATAAACGACTGGACGGAGATTACACAGTTTATCCTGGAGCACCGAGCCAAGGGCTCCTGTAAGTACGCCCTCCCGCTGCGCATCCCCCCGTCAGCCTGCCTCTCCCCCCAGGCCTACCAGCAGGGGGTGACGGTGGACAGCATCGGGATGCTGCCCCGCTCATCCCCGAGACCAGCGCACCGTCGCCGTATACAGCTTGAAGATCGCCGGGTGGCACGGGCCCAAGGCCCCATACACGAGCACCCTGCTGCCCCCGGAGCTGTCCGAGACCCCCAACGCCACGCAGCCAGAACTCGCCCCGGAAGACCCCGAGGATTCGGCCCTCTTGGAGGACCCCGTGGGGACGGTGGCGCCGCAAATCCCACCAAACTGGCACATCCCGTCGATCCAGGACGCCGCGACGCCTTCCATCCCCCGGCCACCCCGAACAACATGGGCCTGATCGCCGGCGCGGTGGGCGGCAGTCTCCTGGCAGCCCTGGTCATTTGCGGAATTGTGTACTGGATGCACCGCCGCACTCGGAAAGCCCCAAAGCGCATACGCCTCCCCCACATCCGGGAAGACGACCAGCCGTCCTCGCACCAGCCCTTGTTTTACTAGATACCCCCCCCTTAATGGGTGCGGGGGGGGTCAGGTCTGCGGGGTTGGGATGGGACCTTAACTCCATATAAAGCGAGTCTGGAAGGGGGGAAAGGCGGACAGTCGATAAGTCGGTAGCGGGGGACGCGCACCTGTTCCGCCTGTCGCACCCACAGCTTTTTCGCGAACCGTCCCGTTTCGGGATGCCGTGCCGCCCGTTGCAGGGCCTGGTGCTCGTGGGCCTCTGGGTCTGTGCCACCAGCCTGGTTGTCCGTGGCCCCACGGTCAGTCTGGTATCAAACTCATTTGTGGACGCCGGGGCCTTGGGGCCCGACGGCGTAGTGGAGGAAGACCTGCTTATTCTCGGGGAGCTTCGCTTTGTGGGGGACCAGGTCCCCCACACCACCTACTACGATGGGGTCGTAGAGCTGTGGCACTACCCCATGGGACACAAATGCCCACGGGTCGTGCATGTCGTCACGGTGACCGCGTGCCCACGTCGCCCCGCCGTGGCATTTGCCCTGTGTCGCGCGACCGACAGCACTCACAGCCCCGCGGTGCGGGGGGGGTCAGGTCTGCGGGGTTGGGATGGGACCTTAACTCCATATAAGCGAGTCGGAGGGGGGAAAGGCGGACAGTCGATAAGTCGGTAGCGGGGGACGCGCACCTGTTCCGCCTGTCGCACCCACAGCTTTTTCGCGAACCGTCCCGTTTCGGGATGCCGTGCCGCCCGTTGCAGGGCCTGGTGCTCGTGGGCCTCTGGGTCTGTGCCACCAGCCTGGTTGTCCGTGGCCCCACGGTCAGTCGGTATCAAACTCATTTGTGGACGCCGGGGCCTTGGGGCCCGACGGCGTAGTGGAGGAAGACCTGCTTATTCTCGGGGAGCTTCGCTTTGTGGGGGACCAGGTCCCCCACACCACCTACTACGATGGGGTCGTAGAGCTGTGGCACTACCCCATGGGACACAAATGCCCACGGGTCGTGCATGTCGTCACGGTGACCGCGTGCCCACGTCGCCCCGCCGTGGCATTTGCCCTGTGTCGCGCGACCGACAGCACTCACAGCCCCGCATATCCCACCCTGGAGCTGAATCTGGCCCAACAGCCGCTTTTGCGGGTCCGGAGGGCGACGCGTGACTATGCCGGGGTGTACGTGTTACGCGTATGGGTCGGGGACGCACCAAACGCCAGCCTGTTTGTCCTGGGGATGGCCATAGCCGCCGAAGGTACTCTGGCGTACAACGGCTCGGCCCATGGCTCCTGCGACCCGAAACTGCTTCCGTCTTCGGCCCCGCGTCTGGCCCCGGCGAGCGTATACCAACCCGCCCCTAACCCGGCCTCCACCCCCTCCACCACCACCTCCCCCCCTCGACCACCACCTCCACCCCCTCGACCACCATCCCCGCTCCCCAAGCATCGACCACACCCTTCCCCACGGGAGACCCAAAACCCCAACCTCACGGGGTCAACCACGAACCCCCATCGAATGCCACGCGAGCGACCCGCGACTCGCGATATGCGCTAACGGTGACCCAGATAATCCAGATAGCCATCCCCGCGTCCATTATAGCCCTGGTGTTTCTGGGGAGCTGTATTTGCTTTATACACAGATGTCAACGCCGCTACCGACGCTCCCGCCGCCCGATTTACAGCCCCCAGATACCCACGGGCATCTCATGCGCGGTGAACGAAGCGGCCATGGCCCGCCTCGGAGCCGAGCTCAAATCGCATCCGAGCACCCCCCCCAAATCCCGGCGCCGGTCGTCACGCACGCCAATGCCCTCCCTGACGGCCATCGCCGAAGAGTCGGAGCCCGCGGGGGCGGCTGGGCTTCCGACGCCCCCCGTGGACCCCACGACATCCCCCCAACGCCTCCCCTGTTGGTATAGGTCCACGGCCACTGGCCGGGGGCACCACATAACCGACCGCAGTCACTGAGTTGGGAATAAACCGGTATTATTTTCCTATATCCGTGTATGTCCATTTCTTTCTTCCCCCCCCCCCCCGGAAACCAAAGAAGGAAGCAAAGAATGGATGGGAGGAGTTCAGGAAGCCGGGGAGAGGGCCCGCGGCGCATTTAAGGCGTTGTTGTGTTGACTTTGGCTCTTCTGGCGGGTTGGTGCGGTGCTGTTTGTTGGGCTCCCATTTTACCCGAAGATCGGCTGCTATCCCCGGGCATGGATCGCGGGGCGGTGGGGGGGCTTCTTCTCGGTGTTTGTGTTGTATCGTGCTTGGCGGGAACGCCCAAAACGTCCTGGAGACGGGTGAGTGTCGGCGAGGACGTTTCGTTGCTTCCACTCGGGGCCTACGGGGCGCGGCCCGACCCAGAAACTACTATGGGCCGTGGAACCCCTGGATGGGTGCGGCCCCTTACACCCGTCGTGGGTCTCGCTGATGCCCCCCAAGCAGGTGCCCGAGACGGTCGTGGATGCGGCGTGCATGCGCGCTCCGGTCCCGCTGGCGATGGCGTACGCCCCCCCGGCCCCATCTGCGACCGGGGGTCTACGAACGGACTTCGTGTGGCAGGAGCGCGCGGCCGTGGTTAACCGGAGTCTGGTTATTCACGGGGTCCGAGAGACGGACAGCGGCCTGTATACCCTGTCCGTGGGCGACATAAAGGACCCGGCTCGCCAAGTGGCCTCGGTGGTCCTGGTGGTGCAACCGGCCCCAGTTCCGACCCCACCCCCGACCCCAGCCGATTACGACGAGGATGACAATGACGAGGGCGAGGACGAAAGTCTCGCCGGCACTCCCGCCAGCGGGACCCCCCGGCTCCCGCCTCCCCCCCCCCCCCGAGGTCTTGGCCCAGCGCCCCCGAAGTCTCACATGTGCGTGGGGTGACCGTGCGTATGGAGACTCCGGAAGCTATCCTGTTTTCCCCCGGGGAGACGTTCAGCACGAACGTCTCCATCCATGCCATCGCCCACGACGACCAGACCTACTCCATGGACGTCGTCTGGTTGAGGTTCGACGTGCCGACCTCGTGTGCCGAGATGCGAATATACGAATCGTGTCTGTATCACCCGCAGCTCCCAGAATGTCTGTCCCCGGCCGACGCGCCGTGCGCCGCGAGTACGTGGACGTCTCGCCTGGCCGTCCGCAGCTACGCGGGGTGTTCCAGAACAAACCCCCCACCGCGCTGTTCGGCCGAGGCTCACATGGAGCCCGTCCCGGGGCTGGCGTGGCAGGCGGCCTCCGTCAATCTGGAGTTCCGGGACGCGTCCCCACAACACTCCGGCCTGTATCTGTGTGTGGTGTACGTCAACGACCATATTCACGCCTGGGGCCACATTACCATCAGCACCGCGGCGCAGTACCGGAACGCGGTGGTGGAACAGCCCCTCCCACAGCGCGGCGCGGATTTGGCCGAGCCCACCCACCCGCACGTCGGGGCCCCTCCCCACGCGCCCCCAACCCACGGCGCCCTGCGGTTAGGGGCGGTGATGGGGGCCGCCCTGCTGCTGTCTGCGCTGGGGTTGTCGGTGTGGGCGTGTATGACCTGTTGGCGCAGGCGTGCCTGGCGGGCGGTTAAAAGCAGGGCCTCGGGTAAGGGGCCCACGTACATTCGCGTGGCCGACAGCGAGCTGTACGCGGACTGGAGCTCGGACAGCGAGGGAGAACGCGACCAGGTCCCGTGGCTGGCCCCCCCGGAGAGACCCGACTCTCCCTCCACCAATGGATCCGGCTTTGAGATCTTATCACCAACGGCTCCGTCTGTATCCCCCGTAGCGACGGGCATCAATCTCGCCGCCAGCTCACAACCTTTGGATCCGGAAGGCCCGATCGCCGTTACTCCCAGGCCTCCGATTCGTCCGTCTTCTGGTAAGGCGCCCCATCCCGAGGCCCCACGTCGGTCGCCGAACTGGGCGACCGCCGGCGAGGTGGACGTCGGAGACGAGCTAATCGCGATTTCCGACGAACGCGGACCCCCCCGACATGACCGCCCGCCCCTCGCCACGTCGACCGCGCCCTCGCCACACCCGCGACCCCCGGGCTACACGGCCGTTGTCTCCCCGATGGCCCTCCGGCTGTCGACGCCCCCTCCCTGTTTGTCGCCTGGCTGGCCGCTCGGTGGCTCCGGGGGGCTTCCGGCCTGGGGGCCGTCCTGTGTGGGATTGCGTGGTATGTGACGTCAATTGCCCGAGGCGCACAAAGGGCCGGTGGTCCGCCTAGCCGCAGCAAATTAAAAATCGTGAGTCACAGCGACCGCAACTTCCCACCCGGAGCTTTCTTCCGGCCTCGATGACGTCCCGGCTCTCCGATCCCAACTCCTCAGCGCGATCCGACATGTCCGTGCCGCTTTATCCCACGGCCTCGCCAGTTTCGGTCGAAGCCTACTACTCGGAAAGCGAAGACGAGGCGGCCAACGACTTCCTCGTACGCATGGGCCGCCAACAGTCGGTATTAAGGCGTTGACGCAGACGCACCCGCTGCGTCGGCATGGTGATCGCCTGTCTCCTCGTGGCCGTTCTGTCGGGCGGATTTGGGGCGCTCCTGATGTGGCTGCTCCGCTAAAAGACCGCATCGACACGCGCGTCCTTCTTGTCGTCTCTCTTCCCCCCCATCACCCCGCAATTTGCACCCAGCCTTTAACTACATTAAATTGGGTTCGATTGGCAATGTTGTCTCCCGGTTGATTTTTGGGTGGGTGGGGAGTGGGT GGGTGGGGAGTGGGTGGGGGAATGGGTGGGSEQ ID NO: 9 is a nucleotide sequence that encodes pSH-tetR.(SEQ ID NO: 9) tcgcgcgtttcggtgatgacggtgaaaacctctgacacatgcagctcccggagacggtcacagcttgtctgtaagcggatgccgggagcagacaagcccgtcagggcgcgtcagcgggtgttggcgggtgtcggggctggcttaactatgcggcatcagagcagattgtactgagagtgcaccatatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgccattcgccattcaggctgcgcaactgttgggaagggcgatcggtgcgggcctcttcgctattacgccagctggcgaaagggggatgtgctgcaaggcgattaagttgggtaacgccagggttttcccagtcacgacgttgtaaaacgacggccagtgccaagcttggctgcaggtcaacaccagagcctgcccaacatggcacccccactcccacgcacccccactcccacgcacccccactcccacgcacccccactcccacgcacccccactcccacgcacccccactcccacgcacccccactcccacgcacccccactcccacgcacccccactcccacgcatccccgcgatacatccaacacagacagggaaaagatacaaaagtaaacctttatttcccaacagacagcaaaaatcccctgagtttttttttattagggccaacacaaaagacccgctggtgtgtggtgcccgtgtctttcacttttcccctccccgacacggattggctggtgtagtgggcgcggccagagaccacccagcgcccgacccccccctccccacaaacacggggggcgtcccttattgttttccctcgtcccgggtcgaccagacatgataagatacattgatgagtttggacaaaccacaactagaatgcagtgaaaaaaatgctttatttgtgaaatttgtgatgctattgctttatttgtaaccattataagctgcaataaacaagttctgctttaataagatctgaattcccgggatccgctgtacgcggacccactttcacatttaagttgtttttctaatccgcatatgatcaattcaaggccgaataagaaggctggctctgcaccttggtgatcaaataattcgatagcttgtcgtaataatggcggcatactatcagtagtaggtgtttccctttcttctttagcgacttgatgctcttgatcttccaatacgcaacctaaagtaaaatgccccacagcgctgagtgcatataatgcattctctagtgaaaaaccttgttggcataaaaaggctaattgattttcgagagtttcatactgtttttctgtaggccgtgtacctaaatgtacttttgctccatcgcgatgacttagtaaagcacatctaaaacttttagcgttattacgtaaaaaatcttgccagctttccccttctaaagggcaaaagtgagtatggtgcctatctaacatctcaatggctaaggcgtcgagcaaagcccgcttattttttacatgccaatacaatgtaggctgctctacacctagcttctgggcgagtttacgggttgttaaaccttcgattccgacctcattaagcagctctaatgcgctgttaatcactttacttttatctaatctagacatatcaattcgccctatagtgagtcgtattacaattctttgccaaaatgatgagacagcacaataaccagcacgttgcccaggagctgtaggaaaaagaagaaggcatgaacatggttagcagaggggcccggtttggactcagagtattttatcctcatctcaaacagtgtatatcattgtaaccataaagagaaaggcaggatgatgaccaggatgtagttgtttctaccaataagaatatttccacgccagccagaatttatatgcagaaatattctaccttatcatttaattataacaattgttctctaaaactgtgctgaagtacaatataatataccctgattgccttgaaaaaaaagtgattagagaaagtacttacaatctgacaaataaacaaaagtgaatttaaaaattcgttacaaatgcaagctaaagtttaacgaaaaagttacagaaaatgaaaagaaaataagaggagacaatggttgtcaacagagtagaaagtgaaagaaacaaaattatcatgagggtccatggtgatacaagggacatcttcccattctaaacaacaccctgaaaactttgccccctccatataacatgaattttacaatagcgaaaaagaaagaacaatcaagggtccccaaactcaccctgaagttctcaggatcgatccggagctttttgcaaaagcctaggcctccaaaaaagcctcttcactacttctggaatagctcagaggccctagaggatccccggcggggtcgtatgcggctggagggtcgcggacggagggtccctgggggtcgcaacgtaggcggggcttctgtggtgatgcggagagggggcggcccgagtctgcctggctgctgcgtctcgctccgagtgccgaggtgcaaatgcgaccagactgtcgggccagggctaacttataccccacgcctttcccctccccaaaggggcggcagtgacgattcccccaatggccgcgcgtcccaggggaggcaggcccaccgcggggcggccccgtccccggggaccaacccggcgcccccaaagaatatcattagcatgcacggcccggcccccgatttgggggcccaacccggtgtcccccaaagaaccccattagcatgcccctcccgccgacgcaacaggggcttggcctgcgtcggtgccccggggcttcccgccttcccgaagaaactcattaccatacccggaaccccaggggaccaatgcgggttcattgagcgacccgcgggccaatgcgcgaggggccgtgtgttccgccaaaaaagcaattagcataacccggaaccccaggggagtggttacgcgcggcgcgggaggcggggaataccggggttgcccattaagggccgcgggaattgccggaagcgggaagggcggccggggccgcccattaatgagtttctaattaccataccgggaagcggaacaaggcctcttgcaagtttttaattaccataccgggaagtgggcggcccggcccattgggcggtaactcccgcccaatgggccgggccccgaagactcggcggacgctggttggccgggccccgccgcgctggcggccgccgattggccagtcccgcccccgaggcggcccgccctgtgagggcgggctggctccaagcgtatatatgcgcggctcctgccatcgtctctccggagagcggcttggtgcggagctcgaattcggtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcacaattccacacaacatacgagccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaattgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcggggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcaatgctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaaggacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaactcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagttttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctcagcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttaccatctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccagccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagctagagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtcgtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaagcggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagcactgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctgagaatagtgtatgcggcgaccgagttgctcttgcccggcgtcaatacgggataataccgcgccacatagcagaactttaaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcgatgtaacccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacaggaaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatattattgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaataggggttccgcgcacatttccccgaaaagtgccacctgacgtctaagaaaccattattatcatgacattaacctataaaaataggcgtatcacgaggccct ttcgtcSEQ ID NO: 10 is a nucleotide sequencethat encodes the open reading frame of UL24 (strain KOS).(SEQ ID NO: 10) atg gccgcgagaa cgcgcagcct ggtcgaacgcagacgcgtgt tgatggcagg ggtacgaagc catacgcgct tctacaaggc gcttgccaaagaggtgcggg agtttcacgc caccaagatc tgcggcacgc tgttgacgct gttaagcgggtcgctgcagg gtcgctcggt gttcgaggcc acacgcgtca ccttaatatg cgaagtggacctgggaccgc gccgccccga ctgcatctgc gtgttcgaat tcgccaatga caagacgctgggcggggttt gtgtcatcat agaactaaag acatgcaaat atatttcttc cggggacaccgccagcaaac gcgagcaacg ggccacgggg atgaagcagc tgcgccactc cctgaagctcctgcagtccc tcgcgcctcc gggtgacaag atagtgtacc tgtgccccgt cctggtgtttgtcgcccaac ggacgctccg cgtcagccgc gtgacccggc tcgtcccgca gaaggtctccggtaatatca ccgcagtcgt gcggatgctc cagagcctgt ccacgtatac ggtccccatggagcctagga cccagcgagc ccgtcgccgc cgcggcggcg ctgcccgggg gtctgcgagcagaccgaaaa ggtcacactc tggggcgcgc gacccgcccg agccagcggc ccgccaggtaccacccgccg accaaacccc cgcctccacg gagggcgggg gggtgcttaa gaggatcgcggcgctcttct gcgtgcccgt ggccaccaag a ccaaa cccc gagctgcctc cgaatgaSEQ ID NO: 11 is a nucleotide sequencethat encodes the open reading frame of gK (strain KOS). (SEQ ID NO: 11)atgctcgccg tccgttccct gcagcacctc tcaaccgtcg tcttgataac ggcgtacggcctcgtgctcg tgtggtacac cgtcttcggt gccagtccgc tgcaccgatg tatttacgcggtacgcccca ccggcaccaa caacgacacc gccctcgtgt ggatgaaaat gaaccagaccctattgtttc tgggggcccc gacgcacccc cccaacgggg gctggcgcaa ccacgcccatatctgctacg ccaatcttat cgcgggtagg gtcgtgccct tccaggtccc acccgacgccacgaatcgtc ggatcatgaa cgtccacgag gcagttaact gtctggagac cctatggtacacacgggtgc gtctggtggt cgtagggtgg ttcctgtatc tggcgttcgt cgccctccaccaacgccgat gtatgtttgg tgtcgtgagt cccgcccaca agatggtggc cccggccacctacctcttga actacgcagg ccgcatcgta tcgagcgtgt tcctgcagta cccctacacgaaaattaccc gcctgctctg cgagctgtcg gtccagcggc aaaacctggt tcagttgtttgagacggacc cggtcacctt cttgtaccac cgccccgcca tcggggtcat cgtaggctgcgagttgatgc tacgctttgt ggccgtgggt ctcatcgtcg gcaccgcttt catatcccggggggcatgtg cgatcacata ccccctgttt ctgaccatca ccacctggtg ttttgtctccaccatcggcc tgacagagct gtattgtatt ctgcggcggg gcccggcccc caagaacgcagacaaggccg ccgccccggg gcgatccaag gggctgtcgg gcgtctgcgg gcgctgttgttccatcatcc tgtcgggcat cgcaatgcga ttgtgttata tcgccgtggt ggccggggtggtgctcgtgg cgcttcacta cgagcaggag at ccagaggc gcctgtttga tgtatga

What is claimed is: 1) An oncolytic Herpes Simplex Virus (HSV)comprising recombinant DNA, wherein the recombinant DNA has both ICP0and ICP34.5 gene product deleted or does not express functional ICP0 andICP34.5 gene product. 2) An oncolytic Herpes Simplex Virus (HSV)comprising recombinant DNA, wherein the recombinant DNA comprises: a) agene comprising a 5′ untranslated region and a HSV-1, or HSV-2, ICP27gene that is operably linked to an ICP27 promoter comprising a TATAelement; b) a tetracycline operator sequence positioned between 6 and 24nucleotides 3′ to said TATA element, wherein the ICP27 gene lies 3′ tosaid tetracycline operator sequence; c) a ribozyme sequence located insaid 5′ untranslated region of said gene; d) a gene sequence encodingtetracycline repressor operably linked to an HSV immediate-earlypromoter, wherein the gene sequence is located at the ICP0 locus; and e)a variant gene that increases syncytium formation as compared to wildtype, wherein the HSV-1, or HSV-2, variant gene is selected from thegroup consisting of: a glycoprotein K (gK) variant; a glycoprotein B(gB) variant; a UL24 variant; and UL20 gene variant, wherein saidoncolytic HSV does not encode functional ICP0 and functional ICP34.5protein. 3) The oncolytic HSV of claim 2, wherein the variant gene is agK variant gene that encodes an amino acid substitution selected fromthe group consisting of: an Ala to Val amino acid substitutioncorresponding to amino acid 40 of SEQ ID NO: 2; an Ala to “x” amino acidsubstitution corresponding to amino acid 40 of SEQ ID NO: 2, wherein “x”is any amino acid; an Asp to Asn amino acid substitution correspondingto amino acid 99 of SEQ ID NO: 2; a Leu to Pro amino acid substitutioncorresponding to amino acid 304 of SEQ ID NO: 2; and an Arg to Leu aminoacid substitution corresponding to amino acid 310 of SEQ ID NO:
 2. 4)The oncolytic HSV of claim 2, wherein the variant gene is a UL24 genethat encodes a Ser to Asn amino acid substitution corresponding to aminoacid 113 of SEQ ID NO:
 3. 5) The oncolytic HSV of claim 3, furthercomprising a variant UL24 gene that encodes a Ser to Asn amino acidsubstitution corresponding to amino acid 113 of SEQ ID NO:
 3. 6) Theoncolytic HSV of any of claims 2-5, wherein the tetracycline operatorsequence comprises two Op2 repressor binding sites. 7) The oncolytic HSVof any of claims 2-6, wherein the ICP27 promoter is an HSV-1 or HSV-2ICP27 promoter. 8) The oncolytic HSV of any of claims 2-7, wherein theimmediate-early promoter is an HSV-1 or HSV-2 immediate-early promoter.9) The oncolytic HSV of any of claims 2-8, wherein the HSVimmediate-early promoter is selected from the group consisting of: ICP0promoter and ICP4 promoter. 10) The oncolytic HSV of any of claims 2-9,wherein the recombinant DNA is part of the HSV-1 genome. 11) Theoncolytic HSV of any of claims 2-9, wherein the recombinant DNA is partof the HSV-2 genome. 12) The oncolytic HSV of any of claims 2-11,further comprising a pharmaceutically acceptable carrier. 13) Theoncolytic HSV of any of claims 1-12, further encoding at least onepolypeptide that can increase the efficacy of the oncolytic HSV toinduce an anti-tumor-specific immunity. 14) The oncolytic HSV of claim13, wherein the at least one polypeptide encodes a product selected fromthe group consisting of: interleukin 2 (IL2), interleukin 12 (IL12),interleukin 15 (IL15), an anti-PD-1 antibody or antibody reagent, ananti-PD-L1 antibody or antibody reagent, an anti-OX40 antibody orantibody reagent, CTLA-4 antibody or antibody reagent, TIM-3 antibody orantibody reagent, and TIGIT antibody or antibody reagent. 15) Acomposition comprising an oncolytic HSV of any of claims 1-14. 16) Thecomposition of claim 15, further comprising a pharmaceuticallyacceptable carrier. 17) A method for treating cancer, the methodcomprising administering the oncolytic HSV of any of claims 1-14 or thecomposition of any of claims 15-16 to a subject having cancer. 18) Themethod of claim 17, wherein the cancer is a solid tumor. 19) The methodof claim 18, wherein the tumor is benign or malignant. 20) The method ofany of claims 17-19, wherein the subject is diagnosed or has beendiagnosed as having cancer is selected from the list consisting of: acarcinoma, a melanoma, a sarcoma, a germ cell tumor, and a blastoma. 21)The method of any of claims 17-19, wherein the subject is diagnosed orhas been diagnosed as having a cancer selected from the group consistingof: non-small-cell lung cancer, breast cancer, brain cancer, coloncancer, prostate cancer, liver cancer, lung cancer, ovarian cancer, skincancer, and pancreatic cancer. 22) The method of any of claims 17-21,wherein the cancer is metastatic. 23) The method of any of claims 17-21,further comprising administering an agent that regulates the tetoperator-containing promoter. 24) The method of claim 23, wherein theagent is doxycycline or tetracycline. 25) The method of claim 23,wherein the agent is administered locally or systemically. 26) Themethod of any of claims 17-25, wherein the oncolytic virus isadministered directly to the tumor.